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Model of MutSα DNA mismatch binding involving a conformational change (A) MutSα scans DNA and (B) initial mismatch binding through MBD6. The insertion of phenylalanine generates the low-affinity DNA-bound state. (C) In a second step, a conformational change occurs. In this step, closing of the MBD2 forms the interface with MBD6 stabilizing the high-affinity DNA-bound state. In all states, MSH2 has ADP bound, while MSH6 is nucleotide-free.
