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-Structure paper
タイトル | The selection process of licensing a DNA mismatch for repair. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 28, Issue 4, Page 373-381, Year 2021 |
掲載日 | 2021年4月5日 |
著者 | Rafael Fernandez-Leiro / Doreth Bhairosing-Kok / Vladislav Kunetsky / Charlie Laffeber / Herrie H Winterwerp / Flora Groothuizen / Alexander Fish / Joyce H G Lebbink / Peter Friedhoff / Titia K Sixma / Meindert H Lamers / |
PubMed 要旨 | DNA mismatch repair detects and removes mismatches from DNA by a conserved mechanism, reducing the error rate of DNA replication by 100- to 1,000-fold. In this process, MutS homologs scan DNA, ...DNA mismatch repair detects and removes mismatches from DNA by a conserved mechanism, reducing the error rate of DNA replication by 100- to 1,000-fold. In this process, MutS homologs scan DNA, recognize mismatches and initiate repair. How the MutS homologs selectively license repair of a mismatch among millions of matched base pairs is not understood. Here we present four cryo-EM structures of Escherichia coli MutS that provide snapshots, from scanning homoduplex DNA to mismatch binding and MutL activation via an intermediate state. During scanning, the homoduplex DNA forms a steric block that prevents MutS from transitioning into the MutL-bound clamp state, which can only be overcome through kinking of the DNA at a mismatch. Structural asymmetry in all four structures indicates a division of labor between the two MutS monomers. Together, these structures reveal how a small conformational change from the homoduplex- to heteroduplex-bound MutS acts as a licensing step that triggers a dramatic conformational change that enables MutL binding and initiation of the repair cascade. |
リンク | Nat Struct Mol Biol / PubMed:33820992 |
手法 | EM (単粒子) |
解像度 | 3.9 - 6.9 Å |
構造データ | EMDB-11791, PDB-7ai5: EMDB-11792, PDB-7ai6: EMDB-11793, PDB-7ai7: EMDB-11794, PDB-7aib: EMDB-11795, PDB-7aic: |
化合物 | ChemComp-ATP: ChemComp-ADP: ChemComp-ANP: |
由来 |
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キーワード | DNA BINDING PROTEIN / DNA Mismatch Repair MutS |