title: Considerations on the folding topology and evolutionary origin of cadherin domains.
abstract: Cell-cell adhesion in zonula adherens and desmosomal junctions is mediated by cadherins, and recent crystal structures of the first domain from murine N-cadherin provide a plausible molecular basis for this adhesive action. A structure-based sequence analysis of this adhesive domain indicates that its fold is common to all extracellular cadherin domains. The cadherin folding topology is also shown to be similar to immunoglobulin-like domains and to other Greek-key beta-sandwich structures, as diverse as domains from plant cytochromes, bacterial cellulases, and eukaryotic transcription factors. Sequence similarities between cadherins and these other molecules are very low, however, and intron patterns are also different. On balance, independent origins for a favorable folding topology seem more likely than evolutionary divergence from an ancestor common to cadherins and immunoglobulins.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: P D
authors.initials: PD
authors.lastname: Kwong
authors.forename: A M
authors.initials: AM
authors.lastname: Fannon
authors.forename: D R
authors.initials: DR
authors.lastname: Colman
authors.forename: W A
authors.initials: WA
authors.lastname: Hendrickson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics; D002448:Cell Adhesion; D003461:Crystallography; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D015820:Cadherins; D007136:Immunoglobulins