title: Dynamic properties of a type II cadherin adhesive domain: implications for the mechanism of strand-swapping of classical cadherins.
abstract: Cadherin-mediated cell adhesion is achieved through dimerization of cadherin N-terminal extracellular (EC1) domains presented from apposed cells. The dimer state is formed by exchange of N-terminal beta strands and insertion of conserved tryptophan indole side chains from one monomer into hydrophobic acceptor pockets of the partner molecule. The present work characterizes individual monomer and dimer states and the monomer-dimer equilibrium of the mouse Type II cadherin-8 EC1 domain using NMR spectroscopy. Limited picosecond-to-nanosecond timescale dynamics of the tryptophan indole moieties for both monomer and dimer states are consistent with well-ordered packing of the N-terminal beta strands intramolecularly and intermolecularly, respectively. However, pronounced microsecond-to-millisecond timescale dynamics of the side chains are observed for the monomer but not the dimer state, suggesting that monomers transiently sample configurations in which the indole moieties are exposed. The results suggest possible kinetic mechanisms for EC1 dimerization.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Vesselin Z
authors.initials: VZ
authors.lastname: Miloushev
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bahna
authors.forename: Carlo
authors.initials: C
authors.lastname: Ciatto
authors.forename: Goran
authors.initials: G
authors.lastname: Ahlsen
authors.forename: Barry
authors.initials: B
authors.lastname: Honig
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Palmer
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D041961:Deuterium Exchange Measurement; D019281:Dimerization; D051379:Mice; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000737:chemistry
chemical_list: D015820:Cadherins; C504541:Cdh8 protein, mouse; D014364:Tryptophan