1ic8
From Proteopedia
(New page: 200px<br /> <applet load="1ic8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ic8, resolution 2.6Å" /> '''HEPATOCYTE NUCLEAR F...) |
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| - | [[Image:1ic8.gif|left|200px]]<br /> | + | [[Image:1ic8.gif|left|200px]]<br /><applet load="1ic8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ic8" size=" | + | |
caption="1ic8, resolution 2.6Å" /> | caption="1ic8, resolution 2.6Å" /> | ||
'''HEPATOCYTE NUCLEAR FACTOR 1A BOUND TO DNA : MODY3 GENE PRODUCT'''<br /> | '''HEPATOCYTE NUCLEAR FACTOR 1A BOUND TO DNA : MODY3 GENE PRODUCT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes | + | Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each contains a homeodomain and a second domain structurally similar to POU-specific domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains create a stable interface that further distinguishes HNF-1alpha from other flexible POU-homeodomain proteins. The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases. |
==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: Diabetes mellitus, insulin-dependent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], Diabetes mellitus, noninsulin-dependent, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], Hepatic adenoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], MODY, type III OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]] | + | Known diseases associated with this structure: Diabetes mellitus, insulin-dependent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], Diabetes mellitus, noninsulin-dependent, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], Hepatic adenoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], MODY, type III OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]], Renal cell carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142410 142410]] |
==About this Structure== | ==About this Structure== | ||
| - | 1IC8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1IC8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IC8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chi, Y-.I.]] | [[Category: Chi, Y-.I.]] | ||
[[Category: Dhe-Paganon, S.]] | [[Category: Dhe-Paganon, S.]] | ||
| - | [[Category: Frantz, J | + | [[Category: Frantz, J D.]] |
[[Category: Hansen, L.]] | [[Category: Hansen, L.]] | ||
[[Category: Oh, B-.C.]] | [[Category: Oh, B-.C.]] | ||
| - | [[Category: Shoelson, S | + | [[Category: Shoelson, S E.]] |
[[Category: transcription regulation; dna-binding; pou domain; diabetes; disease mutation; mody3]] | [[Category: transcription regulation; dna-binding; pou domain; diabetes; disease mutation; mody3]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:10:16 2008'' |
Revision as of 11:10, 21 February 2008
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HEPATOCYTE NUCLEAR FACTOR 1A BOUND TO DNA : MODY3 GENE PRODUCT
Contents |
Overview
Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each contains a homeodomain and a second domain structurally similar to POU-specific domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains create a stable interface that further distinguishes HNF-1alpha from other flexible POU-homeodomain proteins. The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases.
Disease
Known diseases associated with this structure: Diabetes mellitus, insulin-dependent OMIM:[142410], Diabetes mellitus, noninsulin-dependent, 2 OMIM:[142410], Hepatic adenoma OMIM:[142410], MODY, type III OMIM:[142410], Renal cell carcinoma OMIM:[142410]
About this Structure
1IC8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Diabetes mutations delineate an atypical POU domain in HNF-1alpha., Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S, Shoelson SE, Mol Cell. 2002 Nov;10(5):1129-37. PMID:12453420
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