A homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95529
Title:
A homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions.
Authors:
Wibley, J; Deed, Richard W; Jasiok, M; Douglas, K; Norton, John D
Abstract:
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.
Affiliation:
Department of Pharmacy, University of Manchester, UK.
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. Acta
Journal:
Biochimica et Biophysica Acta
Issue Date:
23-May-1996
URI:
http://hdl.handle.net/10541/95529
DOI:
10.1016/0167-4838(96)00008-8
PubMed ID:
8645731
Type:
Article
Language:
en
ISSN:
0006-3002
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWibley, Jen
dc.contributor.authorDeed, Richard Wen
dc.contributor.authorJasiok, Men
dc.contributor.authorDouglas, Ken
dc.contributor.authorNorton, John Den
dc.date.accessioned2010-04-01T16:24:08Z-
dc.date.available2010-04-01T16:24:08Z-
dc.date.issued1996-05-23-
dc.identifier.citationA homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions. 1996, 1294 (2):138-46 Biochim. Biophys. Actaen
dc.identifier.issn0006-3002-
dc.identifier.pmid8645731-
dc.identifier.doi10.1016/0167-4838(96)00008-8-
dc.identifier.urihttp://hdl.handle.net/10541/95529-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.subject.meshBinding Sites-
dc.subject.meshDatabases, Factual-
dc.subject.meshHelix-Loop-Helix Motifs-
dc.subject.meshHumans-
dc.subject.meshInhibitor of Differentiation Protein 1-
dc.subject.meshMacromolecular Substances-
dc.subject.meshMice-
dc.subject.meshModels, Molecular-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMolecular Weight-
dc.subject.meshProtein Structure, Secondary-
dc.subject.meshRepressor Proteins-
dc.subject.meshSequence Homology, Amino Acid-
dc.subject.meshSoftware-
dc.subject.meshTranscription Factors-
dc.titleA homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacy, University of Manchester, UK.en
dc.identifier.journalBiochimica et Biophysica Actaen
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