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Helix-turn-helix

The helix-turn-helix (HTH) motif is a fundamental DNA-binding structural domain in proteins, characterized by two α-helices connected by a short turn of three to four amino acid residues, where the second helix, known as the recognition helix, inserts into the major groove of DNA to enable sequence-specific interactions.^[1] This motif typically forms part of a larger tri-helical bundle that positions the recognition helix for precise binding, allowing proteins to regulate gene expression by recognizing and binding to specific promoter or operator sequences on DNA.^[1] First identified in the early 1980s through crystallographic studies of prokaryotic transcription factors, the HTH motif was recognized as a recurring pattern in proteins like the λ Cro repressor and the 434 repressor, marking it as the inaugural DNA-binding motif to be structurally defined.^[2] Subsequent analyses confirmed its prevalence, with the motif appearing in tens of thousands of proteins across bacteria, archaea, and eukaryotes, underscoring its evolutionary conservation and versatility in transcriptional control.^[3]^[4] In prokaryotes, HTH domains are prominent in repressors and activators such as the Lac repressor and Trp repressor, which modulate operon activity in response to environmental signals.^[1] In eukaryotes, the HTH motif manifests in diverse families, including the homeodomain proteins that guide developmental processes by binding Hox gene regulatory elements, and winged HTH variants like the forkhead transcription factors involved in developmental gene regulation.^[1] Beyond transcription, HTH domains contribute to DNA repair, replication, and even non-DNA functions in some enzymes, highlighting their adaptability.^[3] The motif's simplicity and effectiveness have made it a cornerstone for understanding protein-DNA interactions, with ongoing structural studies revealing subtle variations that fine-tune specificity and affinity.^[5]

Structural Characteristics

Core Architecture

The helix-turn-helix (HTH) motif is a DNA-binding structural motif composed of two α-helices connected by a short β-turn, typically consisting of 3-4 amino acids.^[6] This motif serves as a compact scaffold in many transcription factors, enabling precise interactions with DNA. The overall length of the HTH motif spans approximately 20-25 amino acids, with each α-helix comprising roughly 10-12 residues.^[7] The two α-helices are spatially arranged at an angle of approximately 90 degrees to one another, allowing the motif to adopt a rigid yet adaptable three-dimensional fold.^[6] This perpendicular orientation positions the second helix, often called the recognition helix, parallel to the DNA major groove for potential base-specific contacts. The β-turn is stabilized by a hydrophobic core formed by side-chain interactions between residues in the helices and the turn, enhancing the motif's structural integrity.^[8] Key residues within the turn, such as glycine or proline, confer flexibility, permitting the helices to maintain their relative positioning despite conformational adjustments.^[9] In ribbon diagrams, the HTH topology is characteristically illustrated as two cylindrical helical segments linked by a tight, looped turn, emphasizing the motif's simple yet evolutionarily conserved architecture.^[10]

Functional Components

The helix-turn-helix (HTH) motif's functional components work in concert to enable precise DNA recognition, with the N-terminal scaffold helix providing essential stability and positioning. This helix, often the first or second alpha helix in the motif, anchors the structure through hydrophobic interactions with the protein's core domain, preventing distortion during DNA binding and orienting the motif correctly relative to the DNA major groove. For instance, in the Cro protein from bacteriophage lambda, the scaffold helix forms a bundle with adjacent helices, stabilizing the overall fold via nonpolar contacts.^[1]^[2] The C-terminal recognition helix is the key element for sequence-specific interactions, protruding into the DNA major groove to make direct contacts with nucleotide bases. Side chains from residues like arginine and glutamine extend from this helix to form hydrogen bonds with specific bases, such as arginine contacting guanine in the lambda repressor-operator complex. These interactions, often mediated by water molecules, allow discrimination between DNA sequences, with the helix lying parallel to the base edges in prokaryotic examples. Van der Waals contacts from the recognition helix further enhance affinity by packing against the sugar-phosphate backbone.^[1]^[11]^[12] The turn region, typically comprising three to four residues, acts as a flexible linker that permits independent positioning of the scaffold and recognition helices while maintaining their spatial relationship. This flexibility is crucial for accommodating variations in DNA conformation, with electrostatic interactions and hydrogen bonds between the turn and adjacent helices contributing to motif rigidity. In many HTH variants, the turn exhibits sequence conservation to preserve this balance, though it lacks a strict consensus like Gly-X-Gly across all families.^[1]^[2] Interhelical interactions, primarily hydrophobic packing between the scaffold and recognition helices, ensure the motif's integrity, supplemented by electrostatic forces that fine-tune orientation. Helix lengths and angles show variability across HTH proteins, adapting to diverse DNA sequences and structures; for example, shorter helices in prokaryotic regulators like the trp repressor allow tighter major groove insertion compared to longer eukaryotic homeodomains. This adaptability underscores how the components' functions are tailored for specific biological contexts without altering the core architecture.^[1]^[11]

History of Discovery

Initial Identification

In the late 1970s, sequence analyses of bacterial repressors such as the lac repressor (sequenced in 1973) and trp repressor (sequenced in 1978) began to reveal patterns of conservation within approximately 20-residue segments, hinting at shared structural features among DNA-binding proteins despite limited overall homology. These observations gained traction with the 1982 proposal by Sauer et al., who aligned sequences from the lambda Cro protein and the E. coli catabolite activator protein (CAP), identifying a conserved super-secondary structure consisting of two alpha-helices connected by a short turn, now known as the helix-turn-helix (HTH) motif.^[13] This motif spanned roughly 20 residues and was extended to other repressors like lac and trp, based on similarities in their predicted DNA-binding domains.^[13] A key aspect of this proposal was the identification of invariant residues, particularly in the second helix, that suggested a common DNA-contacting domain capable of inserting into the major groove of DNA for sequence-specific recognition.^[13] Early mutagenesis studies in the 1980s further confirmed the motif's importance; for instance, Sauer et al. (1983) introduced 52 single-amino-acid substitutions in the amino-terminal DNA-binding domain of lambda repressor, demonstrating that changes in residues within the predicted HTH region severely impaired operator binding and specificity.^[14] Although systematic alanine scanning emerged later, these targeted mutations, including alanine replacements at critical positions, underscored the motif's role in DNA interaction.^[14] Supporting evidence came from 1984 NMR data on the lambda repressor, where two-dimensional 1H NMR spectroscopy revealed the flexibility of the N-terminal arm, consistent with its role in DNA wrapping in the repressor-operator complex.^[15]

Structural Determination

The structural determination of the helix-turn-helix (HTH) motif began with the pioneering X-ray crystallographic analysis of the lambda Cro repressor from bacteriophage λ, solved at 3.8 Å resolution in 1981 by Anderson et al. This study provided the first three-dimensional visualization of the HTH motif, revealing two α-helices connected by a short β-turn, with the second helix positioned to interact with the major groove of DNA.^[16] The structure highlighted the motif's compact architecture, where the recognition helix aligns parallel to the DNA backbone, confirming its role as a discrete DNA-binding domain rather than an extended helical segment.^[16] Subsequent crystallographic efforts expanded on this foundation, notably with the 1984 modeling of the catabolite activator protein (CAP) complex with DNA by Weber and Steitz, building on the 1981 CAP protein structure determined by McKay and Steitz at 2.9 Å resolution. This work demonstrated how the HTH motif in CAP inserts into the major groove of B-DNA, with the turn allowing precise positioning of the recognition helix for sequence-specific contacts, thus resolving early uncertainties about groove occupancy. X-ray crystallography remained the dominant technique for these high-resolution static structures, while early NMR spectroscopy in the 1980s began probing the dynamic aspects of HTH motifs, such as conformational flexibility in the turn region during DNA binding. These methods collectively affirmed that the HTH is not a continuous α-helix but features a distinct, flexible turn that enables the motif to adapt to DNA contours without disrupting helical integrity.^[16] A key milestone came in 1987 with the 1.8 Å crystal structure of the trp aporepressor by Zhang et al., including contributions from Otwinowski, which illustrated the symmetric dimerization of the HTH motif and how corepressor binding (tryptophan) stabilizes the structure for operator interaction. This structure further validated the motif's conserved fold across repressors, emphasizing the turn's role in interhelical spacing and dimer interface formation. Another important structure from 1987 was that of the DNA-binding domain of the 434 repressor, which provided additional confirmation of the HTH motif's role in sequence-specific DNA recognition.^[17]^[18]

Functional Mechanism

DNA Binding Process

The DNA binding process of the helix-turn-helix (HTH) motif begins with a nonspecific electrostatic attraction between the positively charged protein surface and the negatively charged phosphate backbone of DNA. This initial approach facilitates rapid association, allowing the protein to scan the DNA via one-dimensional sliding or jumping along the backbone to locate the specific binding site.^[19]^[20] Upon reaching the target sequence, the recognition helix of the HTH motif inserts into the major groove of the DNA double helix, where sequence specificity is achieved through direct interactions between amino acid side chains and nucleotide bases. For instance, arginine residues commonly form bidentate hydrogen bonds with guanine bases, while glutamine or asparagine side chains pair with adenine, enabling precise readout of the DNA sequence without unwinding the helix. These contacts, supplemented by van der Waals interactions and water-mediated bridges, distinguish specific sites from nonspecific ones.^[19]^[21] Binding affinity is enhanced by an induced fit mechanism, in which the DNA undergoes a slight bend of approximately 20 degrees to optimize contacts with the recognition helix, and the protein adjusts its conformation for tighter docking. Dimerization of HTH-containing proteins further promotes cooperative binding, as the symmetric placement of two recognition helices across palindromic or semi-palindromic sites stabilizes the complex through inter-subunit interactions.^[22]^[23]^[24] The kinetics of HTH-DNA association exhibit high specificity, with dissociation constants (K_d) for specific sites typically in the range of 10^{-9} M, as observed for the λ repressor-operator complex. Salt concentration plays a critical role by screening electrostatic interactions; higher ionic strength reduces nonspecific binding affinity more than specific binding, thereby sharpening sequence discrimination.^[25]^[26] The overall binding can be described by the equilibrium:

\text{Protein} + \text{DNA} \rightleftharpoons \text{Complex}

where the association constant K_a = 1 / K_d, and the standard free energy change is given by \Delta G^\circ = -RT \ln K_a, with R as the gas constant and T as temperature in Kelvin. This equation quantifies the thermodynamic favorability of complex formation, derived from the mass action law applied to the binding reaction.^[19]

Role in Transcription

The helix-turn-helix (HTH) motif plays a central role in transcriptional regulation by enabling transcription factors to bind specific DNA sequences near promoters, thereby modulating the initiation of RNA synthesis. Following DNA binding, which positions the HTH motif in the major groove of operator sites, these factors influence the recruitment or occlusion of RNA polymerase (RNAP), determining whether transcription is activated or repressed.^[8] In their activator function, HTH-containing proteins promote transcription through protein-protein interactions that recruit RNAP to the promoter. These interactions often involve additional domains, such as acidic activation regions, that contact RNAP subunits or mediator complexes, stabilizing the pre-initiation complex and enhancing promoter clearance.^[27] This mechanism allows precise temporal and spatial control of gene expression in response to cellular signals.^[8] Conversely, HTH motifs mediate repression by binding operator sites that overlap or are adjacent to the promoter, causing steric hindrance that prevents RNAP from accessing the DNA or forming an open complex. In some cases, repressors with HTH domains bind multiple operator sites to induce DNA looping, which further sequesters the promoter and inhibits transcription initiation. Operator sites typically feature specific sequences recognized by the recognition helix of the HTH motif, with binding affinity modulated by sequence variations.^[9] Combinatorial control arises when multiple HTH-containing factors bind adjacent operator sites, allowing synergistic or antagonistic interactions that fine-tune transcriptional output based on signal integration. This modular arrangement enables robust regulation of gene networks.^[8] Pathologically, mutations in bacterial HTH transcription factors can dysregulate expression of efflux pumps or porins, contributing to antibiotic resistance by altering drug sensitivity.^[25]

Motif Classification

Classic Di-helical Variants

The classic di-helical variant of the helix-turn-helix (HTH) motif represents the simplest form of this DNA-binding structure, comprising exactly two α-helices linked by a short turn of 3-4 amino acids, without any additional folds or extensions. This configuration allows the second helix, known as the recognition helix, to insert into the major groove of DNA, while the first helix stabilizes the motif's position against the DNA backbone. First elucidated in prokaryotic repressors such as the λ Cro protein and λ CI repressor, this variant forms a compact, convex scaffold that facilitates sequence-specific interactions essential for transcriptional control.^[28]^[29] In terms of sequence signature, the motif typically spans 20-25 residues, with the first helix occupying positions 1-10, the intervening turn at positions 11-14, and the recognition helix from positions 15-25. Key conserved residues include alanine or glycine at position 5, glycine at position 9, isoleucine or valine at position 15, and notably glutamine or valine at position 18, which often participates in hydrogen bonding or hydrophobic contacts with DNA bases to confer specificity. These features exhibit low overall sequence conservation across families but are detectable through structural alignments, as demonstrated in early analyses of prokaryotic regulators.^[30] Structurally, the two helices pack against each other at an angle of approximately 20-40 degrees, with hydrophobic interactions stabilizing the core; in oligomeric assemblies, such as those in the lac repressor, additional helix packing occurs via leucine repeats that promote tetramerization and cooperative DNA binding. This variant predominates in prokaryotes and underscores its role as a foundational element in bacterial gene regulation.^[3] Despite its efficiency in simple operator binding, the classic di-helical HTH's limited structural complexity renders it less versatile for the multifaceted, combinatorial regulation typical of eukaryotic systems, where extended motifs enable interactions with co-regulators and chromatin.

Extended and Modified Variants

The helix-turn-helix (HTH) motif has evolved extended and modified forms that incorporate additional helical or beta-structural elements beyond the basic di-helical configuration, enabling greater structural stability, DNA binding affinity, and specificity for regulatory functions. These variants often feature an elaborated tri-helical core or supplementary folds that facilitate more nuanced interactions with DNA grooves, representing adaptations for complex transcriptional control. In eukaryotes, the homeodomain represents a tri-helical HTH variant involved in developmental gene regulation.^[1] Tri-helical variants build on the core HTH by emphasizing the stabilizing role of a third helix in the bundle, which packs against the recognition and scaffold helices to enhance overall domain integrity. In the AraC family, the DNA-binding domain consists of seven alpha helices organized into two subdomains, each containing a tri-helical HTH motif connected by a long central helix (helix 4) that allows rotational flexibility while maintaining stability, with low root-mean-square deviation (RMSD) values indicating a well-folded structure (1.6 Å overall).^[31] This arrangement provides enhanced stability and dimerization capability compared to simpler di-helical forms, supporting high-affinity binding to diverse operator sequences. Tetra-helical variants further extend the structure by adding a C-terminal helix that packs orthogonally against the tri-helical bundle, forming a more compact four-helix arrangement that bolsters hydrophobic core interactions and domain rigidity. In the DeoR family of transcriptional repressors, this tetra-helical configuration is integrated with a phosphosugar isomerase-like ligand-binding domain, allowing precise sensing of metabolic signals and improved DNA affinity through stabilized positioning of the recognition helix in the major groove. Such modifications confer functional advantages, including tighter binding constants and resistance to dissociation under varying cellular conditions, surpassing the baseline affinity of classic di-helical HTH motifs. Winged HTH motifs represent a significant modification where a C-terminal beta-hairpin "wing" (typically two to four antiparallel strands) extends from the helical core, enabling contacts with the DNA minor groove for supplementary sequence recognition. This structure comprises three alpha helices (with the third as the recognition element) flanked by a three-stranded beta-sheet and the wing, as seen in diverse regulators; the wing packs against the helix bundle, increasing specificity by probing adjacent base pairs. Compared to di-helical variants, winged forms exhibit increased binding specificity due to these dual-groove interactions, facilitating finer control in transcription.^[8] Additional modifications include caudal-type extensions with elongated turns between helices, which adjust the geometry for unique DNA docking angles, and sequence-specific beta-hairpin patterns in winged motifs that optimize minor groove insertion. These evolutionary elaborations collectively enhance HTH versatility, with improvements in binding affinity and stability underscoring their role in adapting to diverse genomic contexts without compromising the core motif's simplicity.

Biological Examples

Prokaryotic Instances

The helix-turn-helix (HTH) motif is one of the most abundant DNA-binding domains in prokaryotic transcription factors, enabling precise regulation of gene expression in bacteria and archaea. According to the Pfam database, over 5,000 proteins containing HTH domains have been identified across bacterial genomes, reflecting their critical role in diverse metabolic and stress response pathways. These motifs typically consist of two alpha-helices connected by a short turn, with the second "recognition" helix inserting into the major groove of DNA to facilitate sequence-specific interactions. A seminal example is the Cro repressor from bacteriophage lambda, which uses its HTH motif to bind operator sites in the viral genome, thereby regulating the lysogenic-to-lytic developmental switch. Cro binds preferentially to the right operator (OR3) site, repressing transcription of the cI repressor gene (essential for lysogeny) and promoting lytic growth; its dimeric structure positions two HTH motifs to contact adjacent DNA half-sites with high affinity. This binding is mediated by key residues in the recognition helix, such as glutamine and serine, which form hydrogen bonds with specific bases, as revealed by the crystal structure of the Cro-DNA complex. In Escherichia coli, the Lac repressor (LacI) exemplifies allosteric regulation via an HTH motif, controlling the lactose operon in response to environmental nutrients. The N-terminal DNA-binding domain of LacI contains the HTH, which binds the lac operator DNA sequence to block RNA polymerase access in the absence of lactose; upon inducer (e.g., allolactose) binding to the core domain, a conformational shift disrupts operator affinity, derepressing genes for lactose metabolism. NMR structures of the LacI headpiece-operator complex confirm that the recognition helix makes direct contacts with the major groove, with residues like glutamine 18 and alanine 17 contributing to specificity.^[32] The catabolite activator protein (CAP), also from E. coli, illustrates HTH-mediated activation of sugar metabolism genes under catabolite repression. When bound to cAMP, CAP's C-terminal HTH domains dimerize and bind promoter sites upstream of targets like the lac operon, recruiting RNA polymerase via protein-protein interactions to enhance transcription during glucose scarcity. Crystal structures show the recognition helix (residues 180-185) inserting into the DNA major groove, bending the helix by ~90° to facilitate polymerase binding. The tetracycline repressor (TetR) in Gram-negative bacteria, such as those harboring Tn10 transposons, regulates antibiotic resistance via HTH binding to tet operators. In the apo form, TetR's dimeric HTH motifs bind palindromic operators to repress efflux pump genes (tetA); tetracycline-Mg²⁺ binding induces a conformational change, unwinding helices and ejecting the recognition helices from the DNA, thus derepressing resistance.^[33] High-resolution structures highlight how the HTH orients inversely to other repressors, with residues like arginine 109 stabilizing DNA contacts. These prokaryotic instances predominantly feature classic di-helical HTH variants, underscoring their versatility in microbial adaptation without the modifications seen in more complex systems.

Eukaryotic Instances

In eukaryotes, the helix-turn-helix (HTH) motif serves as a key DNA-binding domain in numerous transcription factors, enabling precise regulation of gene expression in complex multicellular processes such as development, immunity, and signaling.^[8] Genomic surveys of human transcription factors reveal that HTH domains are found in approximately 25% of cases, encompassing diverse families that adapt the motif for eukaryotic-specific functions like tissue differentiation and hormone response.^[34] Homeodomain proteins represent a prominent class of eukaryotic HTH-containing transcription factors, characterized by a ~60-amino-acid domain with three α-helices, where the recognition helix inserts into the major groove of DNA for sequence-specific binding, with the N-terminal arm contacting the minor groove, to regulate developmental genes.^[35] Hox genes, a subset of homeobox genes encoding these proteins, specify anterior-posterior body patterning during embryogenesis across animals.^[36] For instance, the Antennapedia gene in Drosophila melanogaster directs leg formation in thoracic segments; its homeodomain HTH motif recognizes TAAT core sequences in target enhancers, ensuring segment-specific identity, with mutations causing homeotic transformations like leg-to-antenna conversions.^[37]^[36] The ETS family features a winged HTH variant, where an additional beta-sheet "wing" extends from the turn, enhancing protein-protein interactions alongside DNA binding for roles in immune and developmental regulation.^[38] PU.1 (SPI1), an ETS member, is essential for hematopoiesis, driving myeloid and lymphoid lineage commitment by binding 5'-GGAA-3' motifs in promoters of genes like those for colony-stimulating factors.^[39] In multipotent hematopoietic progenitors, PU.1 levels determine cell fate: high expression promotes macrophage differentiation, while moderate levels support B-cell development, underscoring the motif's role in dosage-dependent immune cell specification.^[40] The Myb domain employs a tri-helical HTH structure, with three repeats (R1, R2, R3) each containing an HTH submotif that cooperatively binds DNA to control cell proliferation in both plants and animals.^[41] In animals, B-Myb regulates G2/M cell cycle progression by activating cyclin-dependent kinase genes, with its HTH recognizing AACNG sequences to coordinate mitotic entry.^[42] Plant R2R3-Myb proteins, such as those in Arabidopsis, similarly govern cell cycle transitions and secondary metabolism, adapting the motif for responses to developmental cues like root growth.^[43]

Evolutionary Aspects

Conservation and Origins

The helix-turn-helix (HTH) motif is inferred to have originated in the last universal common ancestor (LUCA), based on its presence in homologous transcription factors across bacteria, archaea, and eukaryotes. Phylogenetic reconstructions indicate that LUCA possessed a basic transcription apparatus including HTH-containing regulators, reflecting the motif's role in early gene regulation mechanisms.^[8] This ancient origin is supported by the motif's detection in diverse prokaryotic lineages, with homologs in both archaeal and bacterial transcription factors suggesting vertical inheritance from LUCA followed by domain-specific adaptations.^[44] Sequence and structural conservation of the HTH motif is profound, particularly in core residues of the recognition helix, which enable DNA binding specificity. In homeodomains—a prominent HTH variant—the third helix (corresponding to positions approximately 42–52 in standard numbering) features highly conserved residues, such as asparagine at position 47 in many Antennapedia-type homeodomains and alanine or other hydrophobic residues at position 51, preserved across eukaryotic phyla and even in prokaryotic counterparts.^[45] These residues maintain >80% identity in key positions across bacterial, archaeal, and eukaryotic regulators, underscoring the motif's structural stability despite billions of years of evolution.^[46] Such invariance highlights the motif's essential function in transcription initiation, with minimal tolerance for variation in the DNA-contacting elements. Phylogenetic analyses trace the HTH motif's diversification to bacterial regulators as the primary root, with subsequent horizontal gene transfer (HGT) events disseminating variants to archaea, including several HTH-containing transcription factor families.^[47] This HGT pattern, combined with vertical descent, explains the motif's ubiquity in prokaryotic genomes predating the archaeal-bacterial divergence around 3.5–4 billion years ago.^[48] Genetic diversification of HTH motifs arose primarily through gene duplication events, including tandem repeats that generated multi-domain architectures and expanded regulatory repertoires in prokaryotes.^[8] These duplications, often coupled with HGT, facilitated functional divergence while preserving the core fold, as seen in the proliferation of HTH variants in bacterial operon regulators.^[49]

Distribution Across Organisms

The helix-turn-helix (HTH) motif is predominantly distributed in prokaryotic organisms, particularly bacteria, where it constitutes a major class of DNA-binding domains in transcription factors. In bacterial genomes such as Escherichia coli, approximately 250 HTH-containing transcription factors have been identified, representing a significant portion of the regulatory proteome and underscoring the motif's role in diverse metabolic and stress responses across bacterial species.^[50] HTH motifs are present in archaea with diversity comparable to bacteria, though archaeal transcription regulators also include alternative DNA-binding architectures like the ribbon-helix-helix fold.^[3]^[51] In eukaryotic organisms, HTH motifs exhibit enrichment in metazoans, where they are integral to developmental processes; for instance, over 200 homeodomain-containing proteins, a subtype of HTH, are encoded in the human genome to regulate gene expression during embryogenesis and tissue differentiation.^[3] This abundance contrasts with fungi, where HTH motifs, primarily in the form of homeodomains, are sparser, with fungal genomes typically encoding fewer than 50 such proteins relative to their overall transcription factor repertoire, reflecting adaptations to simpler multicellular lifestyles.^[52] Viral genomes also incorporate HTH motifs, notably in bacteriophages like lambda, where the CI repressor and Cro proteins utilize HTH structures to bind operator sites and control the switch between lysogenic and lytic cycles during host infection.^[53] Domain-specific adaptations further highlight HTH versatility, such as plant-specific winged HTH variants in heat shock factors that enable targeted responses to abiotic stresses like high temperatures.^[54] These variations build on conserved ancestral patterns, illustrating HTH's broad ecological spread across taxa.^[3]

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Nov 2, 2009 · Animal R1R2R3-MYB proteins have been described for their role in cell cycle regulation mainly at the G1/S, but also at the G2/M transition ...
[40]
The N-terminal DNA-binding 'zinc finger' of the oestrogen ... - PubMed
We suggest that receptor recognition of the HRE is analogous to that of the helix-turn-helix DNA binding motif in that the receptor binds to DNA as a dimer ...
[41]
Chimeric receptors used to probe the DNA-binding ... - PubMed
Apr 15, 1989 · We suggest that receptor recognition of the hormone response element is analogous to that of the helix-turn-helix DNA-binding motif in that ...
[42]
The many faces of the helix-turn-helix domain: Transcription ...
The helix-turn-helix (HTH) domain is a common denominator in basal and specific transcription factors from the three super-kingdoms of life.
[43]
Molecular evolution of the homeodomain family of transcription factors
The 180 bp homeobox region encodes a helix–turn–helix DNA-binding motif known as the homeodomain. ... Sequence signature for each of the homeodomain classes.
[44]
Molecular evolution of the homeodomain family of transcription factors
Members of this family are characterized by a helix–turn–helix DNA-binding motif known as the homeodomain. Homeodomain proteins regulate various cellular ...
[45]
Phylogenetic distribution of DNA-binding transcription factors in ...
In bacteria, 10 families are lost mostly in intracellular pathogens and endosymbionts, while 9 families seem to have been horizontally transferred to archaea.
[46]
Phylogenetic Distribution of DNA-binding Transcription Factors in ...
Horizontal gene transfer and lineage-specific gene losses suggest a progressive elimination of TFs in the course of archaeal and bacterial evolution. This ...
[47]
(PDF) Tracing the birth of structural domains from loops during ...
The structures and functions of proteins are embedded into the loop scaffolds of structural domains. Their origin and evolution remain mysterious.
[48]
A phylogenomic analysis of bacterial helix–turn–helix transcription ...
Mar 1, 2009 · We present here a reassessment of bacterial helix–turn–helix regulator diversity in different organisms from a multidisciplinary perspective, ...
[49]
The hierarchic network of metal-response transcription factors in ...
5) From the E. coli K-12 genome sequence, a total of about 250 species of DNA-binding transcription factor containing a HTH motif have been predicted.
[50]
[PDF] Transcription Regulators in Archaea: Homologies and Differences ...
Sep 20, 2019 · ... less common in archaea, representing 5% of the. 311 total population ... HTH DNA-binding motifs are indicated by red rectangles. 502 ...
[51]
Transcription Factors in Fungi: TFome Dynamics, Three Major ...
Most of the functionally characterized DBD combinations contain an HTH (helix-turn-helix) counterpart, in particular homeodomains (HD; Aravind and Koonin, 1999; ...
[52]
Helix-turn-helix - Wikipedia
The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two α helices, joined by a short strand of amino acids, ...Discovery · Function · Classification of helix-turn... · Winged helix-turn-helix
[53]
The Cro Repressor
Cro (and repressor) contains a helix-turn-helix (HTH) ... Refined Structure of Cro Repressor Protein from Bacteriophage Lambda Suggests Both Flexibility and ...
[54]
Homeobox proteins are essential for fungal differentiation and ...
Apr 8, 2020 · These proteins contain a 60–amino-acid–long homeodomain that contains the DNA-binding helix-turn-helix motif, whereby they bind to their target ...
[55]
The heat shock response in plants: new insights into modes of ... - NIH
Plants have evolved specific temperature preferences, and shifts above this range cause heat stress with detrimental effects such as physiological ...