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Proteolytic E‐cadherin activation followed by solution NMR and X‐ray crystallography
Author(s) -
Häussinger Daniel,
Ahrens Thomas,
Aberle Thomas,
Engel Jürgen,
Stetefeld Jörg,
Grzesiek Stephan
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600192
Subject(s) - division (mathematics) , chemistry , library science , philosophy , classics , computer science , mathematics , history , arithmetic
Cellular adhesion by classical cadherins depends critically on the exact proteolytic removal of their N‐terminal prosequences. In this combined solution NMR and X‐ray crystallographic study, the consequences of propeptide cleavage of an epithelial cadherin construct (domains 1 and 2) were followed at atomic level. At low protein concentration, the N‐terminal processing induces docking of the tryptophan‐2 side‐chain into a binding pocket on the same molecule. At high concentration, cleavage induces dimerization ( K D =0.72 mM, k off =0.7 s −1 ) and concomitant intermolecular exchange of the βA‐strands and the tryptophan‐2 side‐chains. Thus, the cleavage represents the switch from a nonadhesive to the functional form of cadherin.