title: Characterizing the initial encounter complex in cadherin adhesion.
abstract: Cadherins are Ca(2+)-dependent cell-cell adhesion proteins with an extracellular region of five domains (EC1 to EC5). Adhesion is mediated by "strand swapping" of a conserved tryptophan residue in position 2 between EC1 domains of opposing cadherins, but the formation of this structure is not well understood. Using single-molecule fluorescence resonance energy transfer and single-molecule force measurements with the atomic force microscope, we demonstrate that cadherins initially interact via EC1 domains without swapping tryptophan-2 to form a weak Ca(2+) dependent initial encounter complex that has 25% of the bond strength of a strand-swapped dimer. We suggest that cadherin dimerization proceeds via an induced fit mechanism where the monomers first form a tryptophan-2 independent initial encounter complex and then undergo subsequent conformational changes to form the final strand-swapped dimer.
authors: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA. sivasank@iastate.edu
authors: Sanjeevi
authors: S
authors: Sivasankar
authors: Yunxiang
authors: Y
authors: Zhang
authors: W James
authors: WJ
authors: Nelson
authors: Steven
authors: S
authors: Chu
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014162:Transfection; D014364:Tryptophan / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D014364:Tryptophan; D002118:Calcium