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| {{STRUCTURE_1g2z| PDB=1g2z | SCENE= }} | | {{STRUCTURE_1g2z| PDB=1g2z | SCENE= }} |
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| '''DIMERIZATION DOMAIN OF HNF-1ALPHA WITH A LEU 13 SELENOMETHIONINE SUBSTITUTION'''
| | ===DIMERIZATION DOMAIN OF HNF-1ALPHA WITH A LEU 13 SELENOMETHIONINE SUBSTITUTION=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_11106484}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11106484 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11106484}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Selenomethionine]] | | [[Category: Selenomethionine]] |
| [[Category: Transcription factor]] | | [[Category: Transcription factor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:04:26 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 04:20:09 2008'' |