Helix-turn-helix

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The λ repressor of bacteriophage lambda employs a helix-turn-helix (top; green) to bind DNA (bottom; blue and red).

In proteins, the helix-turn-helix (HTH) is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression. Not to be confused with the Basic helix-loop-helix domain

Its discovery was based on similarities between the genes for Cro, CAP, and λ lambda repressor, which share a common 20-25 amino acid sequence that facilitates DNA recognition. In particular, recognition and binding to DNA is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus. In most cases, such as in the Cro repressor, the second helix contributes most to DNA recognition, and hence it is often called the "recognition helix". It binds to the major groove of DNA through a series of hydrogen bonds and various Van der Waals interactions with exposed bases. The other α helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition.

References

Brennan R, Matthews B (1989). "The helix-turn-helix DNA binding motif". J. Biol. Chem. 264 (4): 1903-6. PMID 2644244.

Matthews B, Ohlendorf D, Anderson W, Takeda Y (1982). "Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor". Proc. Natl. Acad. Sci. U.S.A. 79 (5): 1428-32. doi:10.1073/pnas.79.5.1428. PMID 6951187.

External links

Protein secondary structure
Helices:	α-helix \| 3₁₀ helix \| π-helix \| β-helix \| Polyproline helix \| Collagen helix
Extended:	β-strand \| Turn \| Beta hairpin \| Beta bulge \| α-strand
Supersecondary:	Coiled coil \| Helix-turn-helix \| EF hand
Secondary structure propensities of amino acids
Helix-favoring:	Methionine \| Alanine \| Leucine \| Glutamic acid \| Glutamine \| Lysine
Extended-favoring:	Threonine \| Isoleucine \| Valine \| Phenylalanine \| Tyrosine \| Tryptophan
Disorder-favoring:	Glycine \| Serine \| Proline \| Asparagine \| Aspartic acid
No preference:	Cysteine \| Histidine \| Arginine
←Primary structure		Tertiary structure→

v • d • e

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH)	ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP	Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH)	AP-2

(2) Zinc finger
DNA-binding domains

(2.1) Nuclear receptor (Cys₄)	subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys₄	GATA (1, 2, 3, 4, 5, 6)
(2.3) Cys₂His₂	General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys₆	HIVEP1

(3) Helix-turn-helix
domains

(3.1) Homeo domain	ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7)
(3.2) Paired box	PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork head / winged helix	E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3)
(3.4) Heat Shock Factors	HSF1
(3.5) Tryptophan clusters	ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain	transcriptional enhancer factor 1, 2

(4) β-Scaffold factors with
minor groove contacts

(4.1) Rel homology region	NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT	STAT (1, 2, 3, 4, 5, 6)
(4.3) p53	p53
(4.4) MADS box	Mef2 (A, B, C, D) • SRF
(4.7) High mobility group	HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1
(4.10) Cold-shock domain	CSDA

(0) Other
transcription factors

(0.2) HMGI(Y)	HMGA (1, 2)
(0.3) Pocket domain	Rb • RBL1 • RBL2
(0.6) Miscellaneous	ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD