1F93

CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE DIMERIZATION DOMAIN OF HNF-1 ALPHA AND THE COACTIVATOR DCOH

1F93 の概要

• エントリーDOI: 10.2210/pdb1f93/pdb
• 分子名称: DIMERIZATION COFACTOR OF HEPATOCYTE NUCLEAR FACTOR 1-ALPHA, HEPATOCYTE NUCLEAR FACTOR 1-ALPHA (3 entities in total)
• 機能のキーワード: four-helix bundle, transcriptional activator-coactivator complex, dimerization domain, transcription
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cytoplasm: P61459; Nucleus: P22361
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 62180.96

構造登録者

Rose, R.B.,Bayle, J.H.,Endrizzi, J.A.,Cronk, J.D.,Crabtree, G.R.,Alber, T. (登録日: 2000-07-06, 公開日: 2000-09-20, 最終更新日: 2024-10-30)

主引用文献

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

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: 10966642
DOI: 10.1038/78966

実験手法

X-RAY DIFFRACTION (2.6 Å)