Structural and functional insights into the mechanism by which MutS2 recognizes a DNA junction

MutS family proteins are classified into MutS-I and-II lineages: MutS-I recognizes mismatched DNA and ini-tiates 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 un-known 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.

Automated summary

This study reveals the crystal structures of bacterial MutS2 belonging to MutS-II, showing that it has a larger clamp-like inner hole compared to MutS-I and DNA-binding sites at the inner hole are determined by mutagenesis analysis. A model is proposed to describe how MutS2 recognizes DNA junctions.