1g2y
From Proteopedia
(New page: 200px<br /><applet load="1g2y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g2y, resolution 1.00Å" /> '''HNF-1ALPHA DIMERIZAT...) |
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| - | [[Image:1g2y.gif|left|200px]]<br /><applet load="1g2y" size=" | + | [[Image:1g2y.gif|left|200px]]<br /><applet load="1g2y" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1g2y, resolution 1.00Å" /> | caption="1g2y, resolution 1.00Å" /> | ||
'''HNF-1ALPHA DIMERIZATION DOMAIN, WITH SELENOMETHIONINE SUBSTITUED AT LEU 12'''<br /> | '''HNF-1ALPHA DIMERIZATION DOMAIN, WITH SELENOMETHIONINE SUBSTITUED AT LEU 12'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The N-terminal dimerization domain of the transcriptional activator | + | 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 Structure== | ==About this Structure== | ||
| - | 1G2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1G2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G2Y OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Alber, T.]] | [[Category: Alber, T.]] | ||
| - | [[Category: Cronk, J | + | [[Category: Cronk, J D.]] |
| - | [[Category: Endrizzi, J | + | [[Category: Endrizzi, J A.]] |
[[Category: Holton, J.]] | [[Category: Holton, J.]] | ||
| - | [[Category: Rose, R | + | [[Category: Rose, R B.]] |
[[Category: dimerization domain]] | [[Category: dimerization domain]] | ||
[[Category: four-helix bundle]] | [[Category: four-helix bundle]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:45:33 2008'' |
Revision as of 10:45, 21 February 2008
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HNF-1ALPHA DIMERIZATION DOMAIN, WITH SELENOMETHIONINE SUBSTITUED AT LEU 12
Overview
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 Structure
1G2Y is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 12:45:33 2008
