Structure
Volume 30, Issue 7, 7 July 2022, Pages 973-982.e4
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Article
Structural and functional insights into the mechanism by which MutS2 recognizes a DNA junction

https://doi.org/10.1016/j.str.2022.03.014Get rights and content
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Highlights

  • Crystal structure of the core region of a bacterial MutS2

  • MutS2 exhibits a dimeric clamp-shaped structure that resembles MutS

  • Identification of DNA-binding sites on the inner surface of the MutS2 clamp

  • A model for the MutS2-DNA complex is proposed

Summary

MutS family proteins are classified into MutS-I and -II lineages: MutS-I recognizes mismatched DNA and initiates mismatch repair, whereas MutS-II recognizes DNA junctions to modulate recombination. MutS-I forms dimeric clamp-like structures enclosing the mismatched DNA, and its composite ATPase sites regulate DNA-binding modes. Meanwhile, the structures of MutS-II have not been determined; accordingly, it remains unknown how MutS-II recognizes DNA junctions and how nucleotides control DNA binding. Here, we solved the ligand-free and ADP-bound crystal structures of bacterial MutS2 belonging to MutS-II. MutS2 also formed a dimeric clamp-like structure with composite ATPase sites. The ADP-bound MutS2 was more flexible compared to the ligand-free form and could be more suitable for DNA entry. The inner hole of the MutS2 clamp was two times larger than that of MutS-I, and site-directed mutagenesis analyses revealed DNA-binding sites at the inner hole. Based on these, a model is proposed that describes how MutS2 recognizes DNA junctions.

Keywords

DNA recombination
ATPase
MutS family
and X-ray crystallography

Data and code availability

  • The atomic coordinates and structure factor amplitudes of the ligand-free and ADP-bound forms of ttMutS2488 are available at the protein databank (https://www.rcsb.org) under accession numbers 7VUF and 7VUK, respectively.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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