|
|
| (14 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1g39.gif|left|200px]]<br /><applet load="1g39" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1g39, resolution 1.22Å" /> | |
| - | '''WILD-TYPE HNF-1ALPHA DIMERIZATION DOMAIN'''<br /> | |
| | | | |
| - | ==Overview== | + | ==WILD-TYPE HNF-1ALPHA DIMERIZATION DOMAIN== |
| - | 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.
| + | <StructureSection load='1g39' size='340' side='right'caption='[[1g39]], [[Resolution|resolution]] 1.22Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==About this Structure== | + | <table><tr><td colspan='2'>[[1g39]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G39 FirstGlance]. <br> |
| - | 1G39 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=1G39 OCA].
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.22Å</td></tr> |
| - | | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1g39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g39 OCA], [https://pdbe.org/1g39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g39 RCSB], [https://www.ebi.ac.uk/pdbsum/1g39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g39 ProSAT]</span></td></tr> |
| - | ==Reference== | + | </table> |
| - | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11106484 11106484]
| + | == Function == |
| - | [[Category: Single protein]] | + | [https://www.uniprot.org/uniprot/HNF1A_MOUSE HNF1A_MOUSE] Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.<ref>PMID:19289501</ref> <ref>PMID:10966642</ref> |
| - | [[Category: Alber, T.]] | + | == References == |
| - | [[Category: Cronk, J D.]] | + | <references/> |
| - | [[Category: Endrizzi, J A.]] | + | __TOC__ |
| - | [[Category: Holton, J.]] | + | </StructureSection> |
| - | [[Category: Rose, R B.]] | + | [[Category: Large Structures]] |
| - | [[Category: dimerization domain]] | + | [[Category: Mus musculus]] |
| - | [[Category: four-helix bundle]] | + | [[Category: Alber T]] |
| - | [[Category: transcription factor]] | + | [[Category: Cronk JD]] |
| - | | + | [[Category: Endrizzi JA]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:45:33 2008''
| + | [[Category: Holton J]] |
| | + | [[Category: Rose RB]] |
| Structural highlights
Function
HNF1A_MOUSE Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.[1] [2]
References
- ↑ Servitja JM, Pignatelli M, Maestro MA, Cardalda C, Boj SF, Lozano J, Blanco E, Lafuente A, McCarthy MI, Sumoy L, Guigo R, Ferrer J. Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver. Mol Cell Biol. 2009 Jun;29(11):2945-59. doi: 10.1128/MCB.01389-08. Epub 2009 Mar , 16. PMID:19289501 doi:http://dx.doi.org/10.1128/MCB.01389-08
- ↑ Rose RB, Bayle JH, Endrizzi JA, Cronk JD, Crabtree GR, Alber T. Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha. Nat Struct Biol. 2000 Sep;7(9):744-8. PMID:10966642 doi:10.1038/78966
|
