3h4l

From Proteopedia

(Difference between revisions)

Revision as of 02:01, 25 December 2014

Crystal Structure of N terminal domain of a DNA repair protein

Structural highlights

3h4l is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PMS1 (Saccharomyces cerevisiae)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PMS1_YEAST] Required for DNA mismatch repair (MMR), correcting base-base mismatches and insertion-deletion loops (IDLs) resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. Component of the MutLalpha heterodimer that forms a ternary complex with the MutS heterodimers, which initially recognize the DNA mismatches. This complex is thought to be responsible for directing the downsteam MMR events, including strand discrimination, excision, and resynthesis. Plays a major role in maintaining the genetic stability of simple sequence repeats and in the repair of heteroduplex sites present in meiotic recombination intermediates.^[1] ^[2] ^[3]

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

Saccharomyces cerevisiae MutLalpha is a heterodimer of Mlh1 and Pms1 that participates in DNA mismatch repair (MMR). Both proteins have weakly conserved C-terminal regions (CTDs), with the CTD of Pms1 harboring an essential endonuclease activity. These proteins also have conserved N-terminal domains (NTDs) that bind and hydrolyze ATP and bind to DNA. To better understand Pms1 functions and potential interactions with DNA and/or other proteins, we solved the 2.5A crystal structure of yeast Pms1 (yPms1) NTD. The structure is similar to the homologous NTDs of Escherichia coli MutL and human PMS2, including the site involved in ATP binding and hydrolysis. The structure reveals a number of conserved, positively charged surface residues that do not interact with other residues in the NTD and are therefore candidates for interactions with DNA, with the CTD and/or with other proteins. When these were replaced with glutamate, several replacements resulted in yeast strains with elevated mutation rates. Two replacements also resulted in NTDs with decreased DNA binding affinity in vitro, suggesting that these residues contribute to DNA binding that is important for mismatch repair. Elevated mutation rates also resulted from surface residue replacements that did not affect DNA binding, suggesting that these conserved residues serve other functions, possibly involving interactions with other MMR proteins.

Functional residues on the surface of the N-terminal domain of yeast Pms1.,Arana ME, Holmes SF, Fortune JM, Moon AF, Pedersen LC, Kunkel TA DNA Repair (Amst). 2010 Apr 4;9(4):448-57. PMID:20138591^[4]

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

References

↑ Habraken Y, Sung P, Prakash L, Prakash S. ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes. J Biol Chem. 1998 Apr 17;273(16):9837-41. PMID:9545323
↑ Wang TF, Kleckner N, Hunter N. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13914-9. PMID:10570173
↑ Erdeniz N, Dudley S, Gealy R, Jinks-Robertson S, Liskay RM. Novel PMS1 alleles preferentially affect the repair of primer strand loops during DNA replication. Mol Cell Biol. 2005 Nov;25(21):9221-31. PMID:16227575 doi:25/21/9221
↑ Arana ME, Holmes SF, Fortune JM, Moon AF, Pedersen LC, Kunkel TA. Functional residues on the surface of the N-terminal domain of yeast Pms1. DNA Repair (Amst). 2010 Apr 4;9(4):448-57. PMID:20138591 doi:10.1016/j.dnarep.2010.01.010

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/3h4l"

@@ Line 7: / Line 7: @@
 <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=3h4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h4l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3h4l RCSB], [http://www.ebi.ac.uk/pdbsum/3h4l PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PMS1_YEAST PMS1_YEAST]] Required for DNA mismatch repair (MMR), correcting base-base mismatches and insertion-deletion loops (IDLs) resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. Component of the MutLalpha heterodimer that forms a ternary complex with the MutS heterodimers, which initially recognize the DNA mismatches. This complex is thought to be responsible for directing the downsteam MMR events, including strand discrimination, excision, and resynthesis. Plays a major role in maintaining the genetic stability of simple sequence repeats and in the repair of heteroduplex sites present in meiotic recombination intermediates.<ref>PMID:9545323</ref> <ref>PMID:10570173</ref> <ref>PMID:16227575</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3h4l

From Proteopedia

Revision as of 02:01, 25 December 2014

Crystal Structure of N terminal domain of a DNA repair protein

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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