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2lsj

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Revision as of 06:51, 10 September 2015

Solution structure of the mouse Rev1 CTD in complex with the Rev1-interacting Region (RIR)of Pol Kappa

Structural highlights

2lsj is a 2 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2lsg
Gene:	Rev1, Rev1l (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[REV1_MOUSE] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.^[1] [POLK_MOUSE] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity (By similarity).^[2]

Publication Abstract from PubMed

Translesion synthesis is a fundamental biological process that enables DNA replication across lesion sites to ensure timely duplication of genetic information at the cost of replication fidelity, and it is implicated in development of cancer drug resistance after chemotherapy. The eukaryotic Y-family polymerase Rev1 is an essential scaffolding protein in translesion synthesis. Its C-terminal domain (CTD), which interacts with translesion polymerase zeta through the Rev7 subunit and with polymerases kappa, iota, and eta in vertebrates through the Rev1-interacting region (RIR), is absolutely required for function. We report the first solution structures of the mouse Rev1 CTD and its complex with the Pol kappa RIR, revealing an atypical four-helix bundle. Using yeast two-hybrid assays, we have identified a Rev7-binding surface centered at the alpha2-alpha3 loop and N-terminal half of alpha3 of the Rev1 CTD. Binding of the mouse Pol kappa RIR to the Rev1 CTD induces folding of the disordered RIR peptide into a three-turn alpha-helix, with the helix stabilized by an N-terminal cap. RIR binding also induces folding of a disordered N-terminal loop of the Rev1 CTD into a beta-hairpin that projects over the shallow alpha1-alpha2 surface and creates a deep hydrophobic cavity to interact with the essential FF residues juxtaposed on the same side of the RIR helix. Our combined structural and biochemical studies reveal two distinct surfaces of the Rev1 CTD that separately mediate the assembly of extension and insertion translesion polymerase complexes and provide a molecular framework for developing novel cancer therapeutics to inhibit translesion synthesis.

Multifaceted recognition of vertebrate Rev1 by translesion polymerases zeta and kappa.,Wojtaszek J, Liu J, D'Souza S, Wang S, Xue Y, Walker GC, Zhou P J Biol Chem. 2012 Jul 27;287(31):26400-8. doi: 10.1074/jbc.M112.380998. Epub 2012, Jun 14. PMID:22700975^[3]

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

References

↑ Masuda Y, Takahashi M, Fukuda S, Sumii M, Kamiya K. Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein. J Biol Chem. 2002 Jan 25;277(4):3040-6. Epub 2001 Nov 15. PMID:11711549 doi:10.1074/jbc.M110149200
↑ Ogi T, Shinkai Y, Tanaka K, Ohmori H. Polkappa protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15548-53. Epub 2002 Nov 13. PMID:12432099 doi:10.1073/pnas.222377899
↑ Wojtaszek J, Liu J, D'Souza S, Wang S, Xue Y, Walker GC, Zhou P. Multifaceted recognition of vertebrate Rev1 by translesion polymerases zeta and kappa. J Biol Chem. 2012 Jul 27;287(31):26400-8. doi: 10.1074/jbc.M112.380998. Epub 2012, Jun 14. PMID:22700975 doi:10.1074/jbc.M112.380998

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lsj"

@@ Line 2: / Line 2: @@
 <StructureSection load='2lsj' size='340' side='right' caption='[[2lsj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2lsj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LSJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2lsj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LSJ FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lsg|2lsg]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rev1, Rev1l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rev1, Rev1l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2lsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lsj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lsj RCSB], [http://www.ebi.ac.uk/pdbsum/2lsj PDBsum]</span></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=2lsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lsj OCA], [http://pdbe.org/2lsj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lsj RCSB], [http://www.ebi.ac.uk/pdbsum/2lsj PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2lsj" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Liu, J]]
 [[Category: Wojtaszek, J]]

2lsj

From Proteopedia

Revision as of 06:51, 10 September 2015

Solution structure of the mouse Rev1 CTD in complex with the Rev1-interacting Region (RIR)of Pol Kappa

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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