1M7W

HNF4a ligand binding domain with bound fatty acid

Summary for 1M7W

• Entry DOI: 10.2210/pdb1m7w/pdb
• Descriptor: Hepatocyte nuclear factor 4-alpha, LAURIC ACID (3 entities in total)
• Functional Keywords: transcription factor
• Biological source: Rattus rattus (black rat)
• Cellular location: Nucleus: P22449
• Total number of polymer chains: 4
• Total formula weight: 113283.09

Authors

Dhe-Paganon, S.,Duda, K.,Iwamoto, M.,Chi, Y.I.,Shoelson, S.E. (deposition date: 2002-07-22, release date: 2003-07-01, Last modification date: 2024-02-14)

Primary citation

Dhe-Paganon, S.,Duda, K.,Iwamoto, M.,Chi, Y.I.,Shoelson, S.E.
Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand
J.Biol.Chem., 277:37973-37976, 2002

PubMed Abstract: HNF4 alpha is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic beta cells. We have solved the x-ray crystal structure of the HNF4 alpha ligand binding domain, which adopts a canonical fold. Two conformational states are present within each homodimer: an open form with alpha helix 12 (alpha 12) extended and collinear with alpha 10 and a closed form with alpha 12 folded against the body of the domain. Although the protein was crystallized without added ligands, the ligand binding pockets of both closed and open forms contain fatty acids. The carboxylic acid headgroup of the fatty acid ion pairs with the guanidinium group of Arg(226) at one end of the ligand binding pocket, while the aliphatic chain fills a long, narrow channel that is lined with hydrophobic residues. These findings suggest that fatty acids are endogenous ligands for HNF4 alpha and establish a framework for understanding how HNF4 alpha activity is enhanced by ligand binding and diminished by MODY1 mutations.

PubMed: 12193589
DOI: 10.1074/jbc.C200420200

Experimental method

X-RAY DIFFRACTION (2.8 Å)