1F93
CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE DIMERIZATION DOMAIN OF HNF-1 ALPHA AND THE COACTIVATOR DCOH
Summary for 1F93
Entry DOI | 10.2210/pdb1f93/pdb |
Descriptor | DIMERIZATION COFACTOR OF HEPATOCYTE NUCLEAR FACTOR 1-ALPHA, HEPATOCYTE NUCLEAR FACTOR 1-ALPHA (3 entities in total) |
Functional Keywords | four-helix bundle, transcriptional activator-coactivator complex, dimerization domain, transcription |
Biological source | Rattus norvegicus (Norway rat) More |
Cellular location | Cytoplasm: P61459 Nucleus: P22361 |
Total number of polymer chains | 8 |
Total formula weight | 62180.96 |
Authors | Rose, R.B.,Bayle, J.H.,Endrizzi, J.A.,Cronk, J.D.,Crabtree, G.R.,Alber, T. (deposition date: 2000-07-06, release date: 2000-09-20, Last modification date: 2024-10-30) |
Primary citation | Rose, R.B.,Bayle, J.H.,Endrizzi, J.A.,Cronk, J.D.,Crabtree, G.R.,Alber, T. Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha. Nat.Struct.Biol., 7:744-748, 2000 Cited by PubMed Abstract: Maturity-onset diabetes of the young type 3 (MODY3) results from mutations in the transcriptional activator hepatocyte nuclear factor-1alpha (HNF-1alpha). Several MODY3 mutations target the HNF-1alpha dimerization domain (HNF-p1), which binds the coactivator, dimerization cofactor of HNF-1 (DCoH). To define the mechanism of coactivator recognition and the basis for the MODY3 phenotype, we determined the cocrystal structure of the DCoH-HNF-p1 complex and characterized biochemically the effects of MODY3 mutations in HNF-p1. The DCoH-HNF-p1 complex comprises a dimer of dimers in which HNF-p1 forms a unique four-helix bundle. Through rearrangements of interfacial side chains, a single, bifunctional interface in the DCoH dimer mediates both HNF-1alpha binding and formation of a competing, transcriptionally inactive DCoH homotetramer. Consistent with the structure, MODY3 mutations in HNF-p1 reduce activator function by two distinct mechanisms. PubMed: 10966642DOI: 10.1038/78966 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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