Fred Sablitzky, The University of Nottingham, Institute of Genetics, Nottingham, UK
Published online: May 2005
DOI: 10.1038/npg.els.0002713
The helix-loop-helix (HLH) domain is characterized by two sets of amino acid sequences that fold into amphipathic 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
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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. (
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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.
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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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| References | |
| Crews ST (1998) Control of cell lineage-specific development and transcription by bHLH-PAS proteins. Genes and Development 12: 607–620. | |
| Davis RL and Turner DL (2001) Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning. Oncogene 20: 8342–8357. | |
| Ellenberger T, Fass D, Arnaud M and Harrison SC (1994) Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer. Genes and Development 8: 970–980. | |
| Ephrussi A, Church GM, Tonegawa S and Gilbert W (1985) B lineage-specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science 227: 134–140. | |
| Hurst HC (1995) Transcription factors 1: bZIP proteins. Protein Profile 1: 123–168. | |
| Lassar AB, Buskin JN, Lockshon D et al. (1989) MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell 58: 823–831. | |
| Massari ME and Murre C (2000) Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Molecular and Cellular Biology 20: 429–440. | |
| Murre C, McCaw PS and Baltimore D (1989a) A new DNA binding and dimerisation motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 56: 777–783. | |
| Murre C, McCaw PS, Vaessin H et al. (1989b) Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58: 537–544. | |
| Norton JD, Deed RW, Craggs G and Sablitzky F (1998) Id helix-loop-helix proteins in cell growth and differentiation. Trends in Cell Biology 8: 58–65. | |
| Further Reading | |
| book Littlewood TD and Evan GI (1998) "Helix-loop-helix Transcription Factors", 3rd edn. Protein Profile: 1–162. Oxford: Oxford University Press. | |
| ePath http://www.ebi.ac.uk/interpro/. | |
| ePath http://smart.embl-heidelberg.de/. | |
| ePath http://pfam.wustl.edu/. | |
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