1pzl

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{{STRUCTURE_1pzl| PDB=1pzl | SCENE= }}
{{STRUCTURE_1pzl| PDB=1pzl | SCENE= }}
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'''Crystal structure of HNF4a LBD in complex with the ligand and the coactivator SRC-1 peptide'''
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===Crystal structure of HNF4a LBD in complex with the ligand and the coactivator SRC-1 peptide===
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==Overview==
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In addition to suggesting that fatty acids are endogenous ligands, our recent crystal structure of HNF-4alpha showed an unusual degree of structural flexibility in the AF-2 domain (helix alpha12). Although every molecule contained a fatty acid within its ligand binding domain, one molecule in each homodimer was in an open inactive conformation with alpha12 fully extended and colinear with alpha10. By contrast, the second molecule in each homodimer was in a closed conformation with alpha12 folded against the body of the domain in what is widely considered to be the active state. This indicates that although ligand binding is necessary, it is not sufficient to induce an activating structural transition in HNF-4alpha as is commonly suggested to occur for nuclear receptors. To further assess potential mechanisms of activation, we have solved a structure of human HNF-4alpha bound to both fatty acid ligand and a coactivator sequence derived from SRC-1. The mode of coactivator binding is similar to that observed for other nuclear receptors, and in this case, all of the molecules adopt the closed active conformation. We conclude that for HNF-4alpha, coactivator rather than ligand binding locks the active conformation.
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The line below this paragraph, {{ABSTRACT_PUBMED_14982928}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 14982928 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14982928}}
==Disease==
==Disease==
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[[Category: Shoelson, S.]]
[[Category: Shoelson, S.]]
[[Category: Transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:41:06 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:13:59 2008''

Revision as of 18:14, 28 July 2008

Image:1pzl.png

Template:STRUCTURE 1pzl

Contents

Crystal structure of HNF4a LBD in complex with the ligand and the coactivator SRC-1 peptide

Template:ABSTRACT PUBMED 14982928

Disease

Known disease associated with this structure: MODY, type I OMIM:[600281], Diabetes mellitus, noninsulin-dependent OMIM:[600281]

About this Structure

1PZL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for HNF-4alpha activation by ligand and coactivator binding., Duda K, Chi YI, Shoelson SE, J Biol Chem. 2004 May 28;279(22):23311-6. Epub 2004 Feb 24. PMID:14982928

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