Disease relevance of Helix-Turn-Helix Motifs

• Escherichia coli catabolite gene activator protein (CAP) is a helix-turn-helix motif sequence-specific DNA binding protein [de Crombrugghe, B., Busby, S. & Buc, H. (1984) Science 224, 831-838; and Pabo, C. & Sauer, R. (1984) Annu. Rev. Biochem. 53, 293-321] [1].
• Using phenyl-azide-mediated photocrosslinking, we show that the alpha carbon of amino acid 2 of the helix-turn-helix motif of bacteriophage lambda Cro is within 12 A of the bottom-strand nucleotides at positions 2 and 3 of the DNA half site in the Cro-DNA complex in solution [2].
• Trifluoroethanol stabilizes a helix-turn-helix motif in equine infectious-anemia-virus trans-activator protein [3].

High impact information on Helix-Turn-Helix Motifs

• The structure also reveals a helix-turn-helix motif containing an arginine-rich alpha helix that is required for binding to SRP RNA and is implicated in forming the core of an extended RNA binding surface [4].
• Rather, a large hydrophobic surface patch is found in a novel helix-turn-helix motif, which is characteristic of all group II chaperonins including the eukaryotic TRiC/CCT complex [5].
• We investigated the nature of homeodomain-DNA interactions by making a series of mutations in the helix-turn-helix motif of the Drosophila homeodomain protein Paired (Prd) [6].
• The structure provides the first three-dimensional view of a member of the growing IRF family, revealing a new helix-turn-helix motif that latches onto DNA through three of the five conserved tryptophans [7].
• Four of amino acids that directly interact with the DNA are highly conserved: two arginines from the recognition helix lying in the major groove, one lysine from the 'wing' that binds upstream of the core GGAA sequence, and another lysine, from the 'turn' of the 'helix-turn-helix' motif, which binds downstream and on the opposite strand [8].

Chemical compound and disease context of Helix-Turn-Helix Motifs

• The purine repressor protein, PurR, is a member of the lac repressor, LacI, family of Escherichia coli DNA-binding proteins that bind DNA via a highly conserved N-terminal helix-turn-helix motif [9].
• The E. coli trp repressor (trpR) homodimer recognizes its palindromic DNA binding site through a pair of flexible helix-turn-helix (HTH) motifs displayed on an intertwined helical core [10].

Biological context of Helix-Turn-Helix Motifs

• This involves a DNA-binding domain in TFIIB that is distinct from the helix-turn-helix motif (which recognizes an element upstream of the TATA box) [11].
• The NmcR amino acid sequence displays homology with LysR-type transcriptional regulatory proteins, including the conserved residues near its N terminus within a helix-turn-helix motif [12].
• The binding domain is similar to the two tandemly arranged homeodomain-like helix-turn-helix DNA binding motifs of centromere binding protein B. The putative helix-turn-helix motifs of Jerky can also bind double-stranded DNA and represent a novel mammalian RNA/DNA binding domain [13].
• The domain of hMSH4 responsible for the interaction is in the amino-terminal part of the protein whereas the region that contains the ATP binding site and helix-turn-helix motif does not bind to hMLH1 [14].
• Using this method, 12 single substitution mutants (eight in the helix-turn-helix motif region, one in the N-terminal zinc finger region, and three in the C-terminal zinc finger region) were isolated that failed to confer UV resistance in the E. coli strain deleted of the uvrA gene [15].

Associations of Helix-Turn-Helix Motifs with chemical compounds

• The binding of L-tryptophan activates the aporepressor indirectly by fixing the orientation of the second helix of the helix-turn-helix motif and by moulding the details of the repressor's structure near the DNA binding surface [16].
• The three-dimensional crystal structure of met repressor, in the presence or absence of bound corepressor (S-adenosylmethionine), shows a dimer of intertwined monomers, which do not have the helix-turn-helix motif characteristic of other bacterial repressor and activator structures [17].
• These results support the hypothesis that the homeo domain binds to DNA through a helix-turn-helix motif [18].
• We have constructed and analyzed two derivatives of CAP: one having a phenyl azide photoactivatable crosslinking agent at amino acid 2 of the helix-turn-helix motif of CAP, and one having a phenyl azide photoactivatable crosslinking agent at amino acid 10 of the helix-turn-helix motif of CAP [19].
• Structural predictions suggest that the first half of the molecule forms a globular domain of 8 anti-parallel beta-strands with a helix-turn-helix motif at the extreme NH2 terminus [20].

Gene context of Helix-Turn-Helix Motifs

• We report a systematic mutational analysis of the helix-turn-helix motif (HTH) of the fushi tarazu (ftz) homeo domain (HD) of Drosophila [21].
• Changes in the backbone amide proton and nitrogen chemical shifts upon DNA binding have enabled us to experimentally define a DNA-binding surface on the core N-terminal domain of Mbp1 that is associated with a putative winged helix-turn-helix motif [22].
• Secondary structure analysis of the FSHR R265-S296 primary sequence, which has little homology to LHR, predicted a helix-turn-helix motif [23].
• The gntR product is 331 amino acids long, with a helix-turn-helix motif typical of a regulatory protein [24].
• The mutation in strain PAT-2 is the deletion of G at nucleotide 1342 in the patB gene, resulting in the loss of a 62-amino-acid fragment from the C terminus of the PatB protein, including the helix-turn-helix motif [25].

Analytical, diagnostic and therapeutic context of Helix-Turn-Helix Motifs

• Site-directed mutagenesis of the PerA protein suggests that, like VirF, it may use both of its carboxy-terminal helix-turn-helix motifs for DNA interaction, and may also make direct contacts with RNA polymerase [26].
• On the basis of the protein sequence alignment, a DNA-binding alpha helix-beta turn-alpha helix (HTH) motif was identified in the N-terminal region (residues 18-37) of the repressor as well as in the polypeptide of ORF4 (residues 22-41) [27].
• The 1,011-base-pair rafR gene encodes a 336-amino-acid polypeptide containing an N-terminal helix-turn-helix motif. rafO, as defined by in vivo titration of raf repressor, consists of two nearly identical 18-base-pair palindromes that flank the -35 box of the raf promoter [28].
• Sequence analysis of SoxR suggested a helix-turn-helix (HTH) motif at position 87-108 and uncovered an invariant Cys-80 and a cysteine residue at the C-terminus [29].

References