title: Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways.
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.
authors: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, United States.
authors: Beibei
authors: B
authors: Wang
authors: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, United States.
authors: Joshua
authors: J
authors: Francis
authors: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, United States.
authors: Monika
authors: http://orcid.org/0000-0001-9864-3298
authors: M
authors: Sharma
authors: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, United States.
authors: Sean M
authors: SM
authors: Law
authors: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, United States.
authors: Alexander V
authors: http://orcid.org/0000-0002-2750-1599
authors: AV
authors: Predeus
authors: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, United States.
authors: Michael
authors: M
authors: Feig
mesh_terms: D001665:Binding Sites; D002450:Cell Communication / Q000502:physiology; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure*; D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000648:ultrastructure*; D005786:Gene Expression Regulation / Q000502:physiology; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D004247:DNA; D051719:MutS DNA Mismatch-Binding Protein; D045643:DNA Repair Enzymes