title: Thinking outside the cell: how cadherins drive adhesion.
abstract: Cadherins are a superfamily of cell surface glycoproteins whose ectodomains contain multiple repeats of β-sandwich extracellular cadherin (EC) domains that adopt a similar fold to immunoglobulin domains. The best characterized cadherins are the vertebrate 'classical' cadherins, which mediate adhesion via trans homodimerization between their membrane-distal EC1 domains that extend from apposed cells, and assemble intercellular adherens junctions through cis clustering. To form mature trans adhesive dimers, cadherin domains from apposed cells dimerize in a 'strand-swapped' conformation. This occurs in a two-step binding process involving a fast-binding intermediate called the 'X-dimer'. Trans dimers are less flexible than cadherin monomers, a factor that drives junction assembly following cell-cell contact by reducing the entropic cost associated with the formation of lateral cis oligomers. Cadherins outside the classical subfamily appear to have evolved distinct adhesive mechanisms that are only now beginning to be understood.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, 1150 Saint Nicholas Avenue, New York, NY 10032, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Brasch
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Harrison
authors.forename: Barry
authors.initials: B
authors.lastname: Honig
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D011485:Protein Binding
chemical_list: D015820:Cadherins