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5xv8

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Revision as of 08:58, 27 December 2017

Solution structure of the complex between UVSSA acidic region and TFIIH p62 PH domain

Structural highlights

5xv8 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	UVSSA, KIAA1530 (HUMAN), GTF2H1, BTF2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[UVSSA_HUMAN] UV-sensitive syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[UVSSA_HUMAN] Factor involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage. TC-NER allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Acts by promoting stabilization of ERCC6 by recruiting deubiquitinating enzyme USP7 to TC-NER complexes, preventing UV-induced degradation of ERCC6 by the proteasome. Interacts with the elongating form of RNA polymerase II (RNA pol IIo) and facilitates its ubiquitination at UV damage sites, leading to promote RNA pol IIo backtracking to allow access to the nucleotide excision repair machinery. Not involved in processing oxidative damage.^[1] ^[2] ^[3] [TF2H1_HUMAN] Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.

Publication Abstract from PubMed

Nucleotide excision repair is initiated by two different damage recognition subpathways, global genome repair (GGR) and transcription-coupled repair (TCR). In GGR, XPC detects DNA lesions and recruits TFIIH via interaction with the pleckstrin homology (PH) domain of TFIIH subunit p62. In TCR, an elongating form of RNA Polymerase II detects a lesion on the transcribed strand and recruits TFIIH by an unknown mechanism. Here, we found that the TCR initiation factor UVSSA forms a stable complex with the PH domain of p62 via a short acidic string in the central region of UVSSA, and determined the complex structure by NMR. The acidic string of UVSSA binds strongly to the basic groove of the PH domain by inserting Phe408 and Val411 into two pockets, highly resembling the interaction mechanism of XPC with p62. Mutational binding analysis validated the structure and identified residues crucial for binding. TCR activity was markedly diminished in UVSSA -deficient cells expressing UVSSA mutated at Phe408 or Val411. Thus, a common TFIIH recruitment mechanism is shared by UVSSA in TCR and XPC in GGR.

Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways.,Okuda M, Nakazawa Y, Guo C, Ogi T, Nishimura Y Nucleic Acids Res. 2017 Oct 24. doi: 10.1093/nar/gkx970. PMID:29069470^[4]

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

References

↑ Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura K, Ogi T. Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair. Nat Genet. 2012 May;44(5):586-92. doi: 10.1038/ng.2229. PMID:22466610 doi:http://dx.doi.org/10.1038/ng.2229
↑ Schwertman P, Lagarou A, Dekkers DH, Raams A, van der Hoek AC, Laffeber C, Hoeijmakers JH, Demmers JA, Fousteri M, Vermeulen W, Marteijn JA. UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair. Nat Genet. 2012 May;44(5):598-602. doi: 10.1038/ng.2230. PMID:22466611 doi:10.1038/ng.2230
↑ Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K. Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair. Nat Genet. 2012 May;44(5):593-7. doi: 10.1038/ng.2228. PMID:22466612 doi:10.1038/ng.2228
↑ Okuda M, Nakazawa Y, Guo C, Ogi T, Nishimura Y. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways. Nucleic Acids Res. 2017 Oct 24. doi: 10.1093/nar/gkx970. PMID:29069470 doi:http://dx.doi.org/10.1093/nar/gkx970

1 Structural highlights
2 Disease
3 Function
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/5xv8"

@@ Line 3: / Line 3: @@
 <StructureSection load='5xv8' size='340' side='right' caption='[[5xv8]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xv8]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XV8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xv8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XV8 FirstGlance]. <br>
-</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=5xv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xv8 OCA], [http://pdbe.org/5xv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xv8 RCSB], [http://www.ebi.ac.uk/pdbsum/5xv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xv8 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UVSSA, KIAA1530 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GTF2H1, BTF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5xv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xv8 OCA], [http://pdbe.org/5xv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xv8 RCSB], [http://www.ebi.ac.uk/pdbsum/5xv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xv8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Nishimura, Y]]
 [[Category: Okuda, M]]

5xv8

From Proteopedia

Revision as of 08:58, 27 December 2017

Solution structure of the complex between UVSSA acidic region and TFIIH p62 PH domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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