1g2z
DIMERIZATION DOMAIN OF HNF-1ALPHA WITH A LEU 13 SELENOMETHIONINE SUBSTITUTION
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OverviewOverview
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.
About this StructureAbout this Structure
1G2Z is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structure of the HNF-1alpha dimerization domain., Rose RB, Endrizzi JA, Cronk JD, Holton J, Alber T, Biochemistry. 2000 Dec 12;39(49):15062-70. PMID:11106484
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