1pzl
From Proteopedia
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|PDB= 1pzl |SIZE=350|CAPTION= <scene name='initialview01'>1pzl</scene>, resolution 2.1Å | |PDB= 1pzl |SIZE=350|CAPTION= <scene name='initialview01'>1pzl</scene>, resolution 2.1Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=MYR:MYRISTIC ACID'>MYR</scene> | + | |LIGAND= <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= HNF4A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HNF4A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1m7w|1M7W]], [[1lv2|1LV2]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pzl OCA], [http://www.ebi.ac.uk/pdbsum/1pzl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pzl RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: MODY, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600281 600281]], Diabetes mellitus, noninsulin-dependent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600281 600281]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Duda, K.]] | [[Category: Duda, K.]] | ||
[[Category: Shoelson, S.]] | [[Category: Shoelson, S.]] | ||
| - | [[Category: MYR]] | ||
[[Category: transcription]] | [[Category: transcription]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:06:46 2008'' |
Revision as of 20:06, 30 March 2008
| |||||||
| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | HNF4A (Homo sapiens) | ||||||
| Related: | 1M7W, 1LV2
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of HNF4a LBD in complex with the ligand and the coactivator SRC-1 peptide
Contents |
Overview
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.
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
Page seeded by OCA on Sun Mar 30 23:06:46 2008
