Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27768684.
- Also identified by DOI 10.1371/journal.pcbi.1005159 and PMC identifier 5074593.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- DNA
- DNA Repair Enzymes
- MutS DNA Mismatch-Binding Protein