|
|
| Line 1: |
Line 1: |
| - | {{STRUCTURE_4fmo| PDB=4fmo | SCENE= }}
| + | ==Structure of the C-terminal domain of the Saccharomyces cerevisiae MUTL alpha (MLH1/PMS1) heterodimer bound to a fragment of exo1== |
| - | ===Structure of the C-terminal domain of the Saccharomyces cerevisiae MUTL alpha (MLH1/PMS1) heterodimer bound to a fragment of exo1===
| + | <StructureSection load='4fmo' size='340' side='right' caption='[[4fmo]], [[Resolution|resolution]] 3.04Å' scene=''> |
| - | {{ABSTRACT_PUBMED_23435383}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[4fmo]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FMO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FMO FirstGlance]. <br> |
| | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fmn|4fmn]], [[4e4w|4e4w]]</td></tr> |
| | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MLH1, PMS2, YMR167W, YM8520.16 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Saccharomyces cerevisiae S288c]), PMS1, YNL082W, N2317 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Saccharomyces cerevisiae S288c])</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=4fmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fmo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fmo RCSB], [http://www.ebi.ac.uk/pdbsum/4fmo PDBsum]</span></td></tr> |
| | + | </table> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Mismatch-repair factors have a prominent role in surveying eukaryotic DNA-replication fidelity and in ensuring correct meiotic recombination. These functions depend on MutL-homolog heterodimers with Mlh1. In humans, MLH1 mutations underlie half of hereditary nonpolyposis colorectal cancers (HNPCCs). Here we report crystal structures of the MutLalpha (Mlh1-Pms1 heterodimer) C-terminal domain (CTD) from Saccharomyces cerevisiae, alone and in complex with fragments derived from Mlh1 partners. These structures reveal structural rearrangements and additional domains in MutLalpha as compared to the bacterial MutL counterparts and show that the strictly conserved C terminus of Mlh1 forms part of the Pms1 endonuclease site. The structures of the ternary complexes between MutLalpha(CTD) and Exo1 or Ntg2 fragments reveal the binding mode of the MIP-box motif shared by several Mlh1 partners. Finally, the structures provide a rationale for the deleterious impact of MLH1 mutations in HNPCCs. |
| | | | |
| - | ==Function==
| + | Structure of the MutLalpha C-terminal domain reveals how Mlh1 contributes to Pms1 endonuclease site.,Gueneau E, Dherin C, Legrand P, Tellier-Lebegue C, Gilquin B, Bonnesoeur P, Londino F, Quemener C, Le Du MH, Marquez JA, Moutiez M, Gondry M, Boiteux S, Charbonnier JB Nat Struct Mol Biol. 2013 Apr;20(4):461-8. doi: 10.1038/nsmb.2511. Epub 2013 Feb , 24. PMID:23435383<ref>PMID:23435383</ref> |
| - | [[http://www.uniprot.org/uniprot/MLH1_YEAST MLH1_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 different MutL heterodimers that form 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, the repair of heteroduplex sites present in meiotic recombination intermediates, and the promotion of meiotic crossing-over.<ref>PMID:9545323</ref> <ref>PMID:10570173</ref> <ref>PMID:12529393</ref> [[http://www.uniprot.org/uniprot/EXO1_YEAST EXO1_YEAST]] 5'->3' double-stranded DNA exonuclease involved in mismatch repair and eventually also in mitotic recombination between direct repeats. Also has a minor role in the correction of large DNA mismatches that occur in the heteroduplex DNA during meiotic recombination at the HIS4 locus.<ref>PMID:9207118</ref> <ref>PMID:9111347</ref> <ref>PMID:11102356</ref> <ref>PMID:15629726</ref> [[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>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[4fmo]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FMO OCA].
| + | </div> |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:023435383</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Saccharomyces cerevisiae s288c]] | | [[Category: Saccharomyces cerevisiae s288c]] |
| - | [[Category: Charbonnier, J B.]] | + | [[Category: Charbonnier, J B]] |
| - | [[Category: Gueneau, E.]] | + | [[Category: Gueneau, E]] |
| - | [[Category: Legrand, P.]] | + | [[Category: Legrand, P]] |
| | [[Category: Dna damage]] | | [[Category: Dna damage]] |
| | [[Category: Dna repair]] | | [[Category: Dna repair]] |
| Structural highlights
4fmo is a 3 chain structure with sequence from Saccharomyces cerevisiae s288c. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 4fmn, 4e4w |
| Gene: | MLH1, PMS2, YMR167W, YM8520.16 (Saccharomyces cerevisiae S288c), PMS1, YNL082W, N2317 (Saccharomyces cerevisiae S288c) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
Mismatch-repair factors have a prominent role in surveying eukaryotic DNA-replication fidelity and in ensuring correct meiotic recombination. These functions depend on MutL-homolog heterodimers with Mlh1. In humans, MLH1 mutations underlie half of hereditary nonpolyposis colorectal cancers (HNPCCs). Here we report crystal structures of the MutLalpha (Mlh1-Pms1 heterodimer) C-terminal domain (CTD) from Saccharomyces cerevisiae, alone and in complex with fragments derived from Mlh1 partners. These structures reveal structural rearrangements and additional domains in MutLalpha as compared to the bacterial MutL counterparts and show that the strictly conserved C terminus of Mlh1 forms part of the Pms1 endonuclease site. The structures of the ternary complexes between MutLalpha(CTD) and Exo1 or Ntg2 fragments reveal the binding mode of the MIP-box motif shared by several Mlh1 partners. Finally, the structures provide a rationale for the deleterious impact of MLH1 mutations in HNPCCs.
Structure of the MutLalpha C-terminal domain reveals how Mlh1 contributes to Pms1 endonuclease site.,Gueneau E, Dherin C, Legrand P, Tellier-Lebegue C, Gilquin B, Bonnesoeur P, Londino F, Quemener C, Le Du MH, Marquez JA, Moutiez M, Gondry M, Boiteux S, Charbonnier JB Nat Struct Mol Biol. 2013 Apr;20(4):461-8. doi: 10.1038/nsmb.2511. Epub 2013 Feb , 24. PMID:23435383[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gueneau E, Dherin C, Legrand P, Tellier-Lebegue C, Gilquin B, Bonnesoeur P, Londino F, Quemener C, Le Du MH, Marquez JA, Moutiez M, Gondry M, Boiteux S, Charbonnier JB. Structure of the MutLalpha C-terminal domain reveals how Mlh1 contributes to Pms1 endonuclease site. Nat Struct Mol Biol. 2013 Apr;20(4):461-8. doi: 10.1038/nsmb.2511. Epub 2013 Feb , 24. PMID:23435383 doi:10.1038/nsmb.2511
|
