A homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions.
Affiliation
Department of Pharmacy, University of Manchester, UK.Issue Date
1996-05-23
Metadata
Show full item recordAbstract
The function of the dominant negative Id (inhibitor of differentiation) helix-loop-helix (HLH) proteins is to dimerize with, and prevent the DNA binding of basic HLH (bHLH) transcription factors. A three-dimensional homology model was constructed for the HLH domain of human Id3 based on the X-ray crystal structures of the E47, MyoD, and Max bHLH proteins. The model showed that, in contrast to bHLH proteins, Id proteins appear able to dimerize without DNA stabilization because of better packing of the hydrophobic core, and the absence of destabilizing polar loop residues and of repulsive positive charges in the monomer interface at the base of the four alpha-helix bundle. This prediction was tested by in vitro protein-binding experiments, which showed that Id3 did indeed self-associate. It also showed that the inability of Id proteins to bind DNA arises from the non-basic, poorly defined, random coil structure of the region corresponding to that responsible for bHLH DNA-binding. A model of the Id1 protein was constructed and revealed a potential site of charge-charge repulsion in the hypothetical homodimer interface that may explain its observed inability to form homodimers.Citation
A homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions. 1996, 1294 (2):138-46 Biochim. Biophys. ActaJournal
Biochimica et Biophysica ActaDOI
10.1016/0167-4838(96)00008-8PubMed ID
8645731Type
ArticleLanguage
enISSN
0006-3002ae974a485f413a2113503eed53cd6c53
10.1016/0167-4838(96)00008-8
Scopus Count
Collections
Related articles
- The expression pattern of Id4, a novel dominant negative helix-loop-helix protein, is distinct from Id1, Id2 and Id3.
- Authors: Riechmann V, van Crüchten I, Sablitzky F
- Issue date: 1994 Mar 11
- Identification in a fish species of two Id (inhibitor of DNA binding/differentiation)-related helix-loop-helix factors expressed in the slow oxidative muscle fibers.
- Authors: Rescan PY
- Issue date: 1997 Aug 1
- Self-recognition behavior of a helix-loop-helix domain by a fragment scan.
- Authors: Beisswenger M, Cabrele C
- Issue date: 2014 Sep
- The E2A and tal-1 helix-loop-helix proteins associate in vivo and are modulated by Id proteins during interleukin 6-induced myeloid differentiation.
- Authors: Voronova AF, Lee F
- Issue date: 1994 Jun 21
- Phosphorylation of helix-loop-helix proteins ID1, ID2 and ID3.
- Authors: Nagata Y, Shoji W, Obinata M, Todokoro K
- Issue date: 1995 Feb 27