1g2z: Difference between revisions

Revision as of 13:45, 21 February 2008

DIMERIZATION DOMAIN OF HNF-1ALPHA WITH A LEU 13 SELENOMETHIONINE SUBSTITUTION

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

Page seeded by OCA on Thu Feb 21 12:45:30 2008

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OCA

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-[[Image:1g2z.gif|left|200px]]<br /><applet load="1g2z" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1g2z.gif|left|200px]]<br /><applet load="1g2z" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1g2z, resolution 1.15&Aring;" />
 '''DIMERIZATION DOMAIN OF HNF-1ALPHA WITH A LEU 13 SELENOMETHIONINE SUBSTITUTION'''<br />
 ==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.
+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==
-G2Z 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1G2Z OCA].
+G2Z 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=1G2Z OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Single protein]]
 [[Category: Alber, T.]]
-[[Category: Cronk, J.D.]]
+[[Category: Cronk, J D.]]
-[[Category: Endrizzi, J.A.]]
+[[Category: Endrizzi, J A.]]
 [[Category: Holton, J.]]
-[[Category: Rose, R.B.]]
+[[Category: Rose, R B.]]
 [[Category: dimerization domain]]
 [[Category: four-helix bundle]]
@@ Line 22: / Line 22: @@
 [[Category: transcription factor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:39:30 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:45:30 2008''