1PZL

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

Summary for 1PZL

• Entry DOI: 10.2210/pdb1pzl/pdb
• Related: 1LV2 1M7W
• Descriptor: Hepatocyte nuclear factor 4-alpha, steroid receptor coactivator-1, MYRISTIC ACID, ... (4 entities in total)
• Functional Keywords: transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P41235
• Total number of polymer chains: 2
• Total formula weight: 28578.26

Authors

Duda, K.,Chi, Y.-I.,Dhe-paganon, S.,Shoelson, S. (deposition date: 2003-07-11, release date: 2004-06-01, Last modification date: 2024-02-14)

Primary citation

Duda, K.,Chi, Y.-I.,Shoelson, S.
Structural Basis for HNF-4alpha Activation by Ligand and Coactivator Binding
J.Biol.Chem., 279:23311-23316, 2004

PubMed Abstract: 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.

PubMed: 14982928
DOI: 10.1074/jbc.M400864200

Experimental method

X-RAY DIFFRACTION (2.1 Å)