Allosteric cross talk between cadherin extracellular domains.
Atomic force microscopy and surface force apparatus measurements determined the functional impact of the cadherin point mutation W2A and domain deletion mutations on C-cadherin binding signatures. Direct comparison of results obtained using both experimental approaches demonstrates that C-cadherin ectodomains form multiple independent bonds that require different structural regions. The results presented reveal significant interdomain cross talk. They further demonstrate that the mutation W2A not only abolishes adhesion between N-terminal domains, but allosterically modulates other binding states that require functional domains distal to the N-terminal binding site. Such allosteric effects may play a prominent role in modulating adhesion by Type I classic cadherins, cadherin oligomerization at junctional contacts, and propagation of binding information to the cytoplasmic region.
Shi
Quanming
Q
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Maruthamuthu
Venkat
V
Li
Fang
F
Leckband
Deborah
D
D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D018625:Microscopy, Atomic Force; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
D015820:Cadherins