1LV2

Hepatocyte Nuclear Factor 4 is a Transcription Factor that Constitutively Binds Fatty Acids

Summary for 1LV2

• Entry DOI: 10.2210/pdb1lv2/pdb
• Descriptor: Hepatocyte nuclear factor 4-gamma, PALMITIC ACID (3 entities in total)
• Functional Keywords: diabetes, fatty acids, hnf4, mody, nuclear receptor, transcription factor, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q14541
• Total number of polymer chains: 1
• Total formula weight: 26111.35

Authors

Wisely, B.,Miller, A.B.,Davis, R.G.,Spitzer, T.,Shearer, B.,Moore, J.T.,Johnson, R.,Sefler, A.,Willson, T.M.,Williams, S.P. (deposition date: 2002-05-24, release date: 2002-12-18, Last modification date: 2024-04-03)

Primary citation

Wisely, G.B.,Miller, A.B.,Davis, R.G.,Jr Thornquest, A.D.,Johnson, R.,Spitzer, T.,Sefler, A.,Shearer, B.,Moore, J.T.,Willson, T.M.,Williams, S.P.
Hepatocyte Nuclear Factor 4 Is a Transcription Factor that Constitutively Binds Fatty Acids.
Structure, 10:1225-1234, 2002

PubMed Abstract: The 2.7 A X-ray crystal structure of the HNF4gamma ligand binding domain (LBD) revealed the presence of a fatty acid within the pocket, with the AF2 helix in a conformation characteristic of a transcriptionally active nuclear receptor. GC/MS and NMR analysis of chloroform/methanol extracts from purified HNF4alpha and HNF4gamma LBDs identified mixtures of saturated and cis-monounsaturated C14-18 fatty acids. The purified HNF4 LBDs interacted with nuclear receptor coactivators, and both HNF4 subtypes show high constitutive activity in transient transfection assays, which was reduced by mutations designed to interfere with fatty acid binding. The endogenous fatty acids did not readily exchange with radiolabeled palmitic acid, and all attempts to displace them without denaturing the protein failed. Our results suggest that the HNF4s may be transcription factors that are constitutively bound to fatty acids.

PubMed: 12220494
DOI: 10.1016/S0969-2126(02)00829-8

Experimental method

X-RAY DIFFRACTION (2.7 Å)