1G39

WILD-TYPE HNF-1ALPHA DIMERIZATION DOMAIN

Summary for 1G39

• Entry DOI: 10.2210/pdb1g39/pdb
• Related: 1F93 1G2Y 1G2Z
• Descriptor: HEPATOCYTE NUCLEAR FACTOR 1-ALPHA (2 entities in total)
• Functional Keywords: dimerization domain, four-helix bundle, transcription factor, transcription
• Cellular location: Nucleus: P22361
• Total number of polymer chains: 4
• Total formula weight: 13547.80

Authors

Rose, R.B.,Endrizzi, J.A.,Cronk, J.D.,Holton, J.,Alber, T. (deposition date: 2000-10-23, release date: 2001-01-17, Last modification date: 2024-04-03)

Primary citation

Rose, R.B.,Endrizzi, J.A.,Cronk, J.D.,Holton, J.,Alber, T.
High-resolution structure of the HNF-1alpha dimerization domain.
Biochemistry, 39:15062-15070, 2000

PubMed Abstract: The N-terminal dimerization domain of the transcriptional activator hepatocyte nuclear factor-1alpha (HNF-1alpha) is essential for DNA binding and association of the transcriptional coactivator, DCoH (dimerization cofactor of HNF-1). To investigate the basis for dimerization of HNF-1 proteins, we determined the 1.2 A resolution X-ray crystal structure of the dimerization domain of HNF-1alpha (HNF-p1). Phasing was facilitated by devising a simple synthesis for Fmoc-selenomethionine and substituting leucine residues with selenomethionine. The HNF-1 dimerization domain forms a unique, four-helix bundle that is preserved with localized conformational shifts in the DCoH complex. In three different crystal forms, HNF-p1 displays subtle shifts in the conformation of the interhelix loop and the crossing angle between the amino- and carboxyl-terminal helices. In all three crystal forms, the HNF-p1 dimers pair through an exposed hydrophobic surface that also forms the binding site for DCoH. Conserved core residues in the dimerization domain of the homologous transcriptional regulator HNF-1beta rationalize the functional heterodimerization of the HNF-1alpha and HNF-1beta proteins. Mutations in HNF-1alpha are associated with maturity-onset diabetes of the young type 3 (MODY3), and the structure of HNF-p1 provides insights into the effects of three MODY3 mutations.

PubMed: 11106484
DOI: 10.1021/bi001996t

Experimental method

X-RAY DIFFRACTION (1.22 Å)