1f93

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(Difference between revisions)

Revision as of 09:47, 21 July 2021

CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE DIMERIZATION DOMAIN OF HNF-1 ALPHA AND THE COACTIVATOR DCOH

Structural highlights

1f93 is a 8 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PHS_RAT] Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity.^[1] ^[2] [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'.^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Maturity-onset diabetes of the young type 3 (MODY3) results from mutations in the transcriptional activator hepatocyte nuclear factor-1alpha (HNF-1alpha). Several MODY3 mutations target the HNF-1alpha dimerization domain (HNF-p1), which binds the coactivator, dimerization cofactor of HNF-1 (DCoH). To define the mechanism of coactivator recognition and the basis for the MODY3 phenotype, we determined the cocrystal structure of the DCoH-HNF-p1 complex and characterized biochemically the effects of MODY3 mutations in HNF-p1. The DCoH-HNF-p1 complex comprises a dimer of dimers in which HNF-p1 forms a unique four-helix bundle. Through rearrangements of interfacial side chains, a single, bifunctional interface in the DCoH dimer mediates both HNF-1alpha binding and formation of a competing, transcriptionally inactive DCoH homotetramer. Consistent with the structure, MODY3 mutations in HNF-p1 reduce activator function by two distinct mechanisms.

Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha.,Rose RB, Bayle JH, Endrizzi JA, Cronk JD, Crabtree GR, Alber T Nat Struct Biol. 2000 Sep;7(9):744-8. PMID:10966642^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mendel DB, Khavari PA, Conley PB, Graves MK, Hansen LP, Admon A, Crabtree GR. Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. Science. 1991 Dec 20;254(5039):1762-7. PMID:1763325
↑ Hauer CR, Rebrin I, Thony B, Neuheiser F, Curtius HC, Hunziker P, Blau N, Ghisla S, Heizmann CW. Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence. J Biol Chem. 1993 Mar 5;268(7):4828-31. PMID:8444860
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1f93"

@@ Line 3: / Line 3: @@
 <StructureSection load='1f93' size='340' side='right'caption='[[1f93]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1f93]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1F93 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1f93]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F93 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f93 OCA], [http://pdbe.org/1f93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1f93 RCSB], [http://www.ebi.ac.uk/pdbsum/1f93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1f93 ProSAT]</span></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=1f93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f93 OCA], [https://pdbe.org/1f93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f93 RCSB], [https://www.ebi.ac.uk/pdbsum/1f93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f93 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PHS_RAT PHS_RAT]] Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity.<ref>PMID:1763325</ref> <ref>PMID:8444860</ref>  [[http://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>
+[[https://www.uniprot.org/uniprot/PHS_RAT PHS_RAT]] Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity.<ref>PMID:1763325</ref> <ref>PMID:8444860</ref>  [[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1f93

From Proteopedia

Revision as of 09:47, 21 July 2021

CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE DIMERIZATION DOMAIN OF HNF-1 ALPHA AND THE COACTIVATOR DCOH

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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