Protein Motifs: the Helix‐Loop‐Helix Motif


The helix‐loop‐helix (HLH) domain is characterized by two sets of amino acid sequences that fold into amphipathic α helices separated by a flexible linker or ‘loop’ of variable amino acid sequence and length. The HLH domain is a dimerization domain that allows proteins to form homo‐ and/or heterodimers.

Keywords: homo‐ and heterodimers; basic DNA‐binding domain; e box; leucine zipper; PAS domain

Figure 1.

Amino acid sequence alignment of basic helix‐loop‐helix (bHLH) domains. (a) Amino acid sequence (one‐letter code) alignment of Mus musculus (Mus) E12, E47 and MyoD, Drosophila (Dro) Daughterless (Da), Twist and Achaete Scute (As‐c sc and As‐c ac) and Homo sapiens (Hum) N‐myc, L‐myc and C‐myc bHLH domains. Conserved amino acid residues are highlighted in yellow. The basic region, helix 1 and 2 as well as the loop region are indicated. Dots represent gaps in the amino acid sequence alignment. Adapted from Murre et al.. (b) Amino acid sequence alignment of SCL/tal1 bHLH domains derived from Homo sapiens (Hum), Mus musculus (Mus), Gallus gallus (Chi), Xenopus laevis (Xen), Ambystoma mexicanum (Axo), Danio rerio (Zeb) and Takifugu rubripes (Puf). Identical amino acid residues are highlighted in yellow. Database accession numbers are as indicated. Dots represent gaps in the amino acid sequence alignment.

Figure 2.

Tertiary structure of a basic helix‐loop‐helix (bHLH) dimer that binds DNA. Schematic representation of a bHLH dimer exhibits the parallel four helix bundle which allows the basic regions to bind the major groove of the DNA. The N‐terminal (N) as well as C‐terminal (C) end of the bHLH domain is indicated.

Figure 3.

Subdivision of helix‐loop‐helix (HLH) proteins into seven classes. Summary of class, examples and schematic domain structure of HLH proteins (not drawn to scale) as indicated.



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Further Reading

Littlewood TD and Evan GI (1998) Helix‐loop‐helix Transcription Factors, 3rd edn. Protein Profile: 1–162. Oxford: Oxford University Press.


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How to Cite close
Sablitzky, Fred(May 2005) Protein Motifs: the Helix‐Loop‐Helix Motif. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0002713]