Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways

Allostery is conformation regulation by propagating a signal from one site to another distal site. This study focuses on the long-range communication in DNA mismatch repair proteins MutS and its homologs where intramolecular signaling has to travel over 70 Å to couple lesion detection to ATPase activity and eventual downstream repair. Using dynamic network analysis based on extensive molecular dynamics simulations, multiple preserved communication pathways were identified that would allow such long-range signaling. The pathways appear to depend on the nucleotides bound to the ATPase domain as well as the type of DNA substrate consistent with previously proposed functional cycles of mismatch recognition and repair initiation by MutS and homologs. A mechanism is proposed where pathways are switched without major conformational rearrangements allowing for efficient long-range signaling and allostery.

• Publication year

  2016

• Venue

  PLoS Comput. Biol.

• Publication date

  2016-10-01

• Fields of study

  Biology, Medicine, Chemistry, Computer Science

• Identifiers
  DOI 10.1371/journal.pcbi.1005159PMID 27768684PMCID 5074593
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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