Proteolytic E-cadherin activation followed by solution NMR and X-ray crystallography.
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 (KD=0.72 mM, k(off)=0.7 s(-1)) and concomitant intermolecular exchange of the betaA-strands and the tryptophan-2 side-chains. Thus, the cleavage represents the switch from a nonadhesive to the functional form of cadherin.
Häussinger
Daniel
D
Division of Structural Biology, Biozentrum, University of Basel, Basel, Switzerland.
Ahrens
Thomas
T
Aberle
Thomas
T
Engel
Jürgen
J
Stetefeld
Jörg
J
Grzesiek
Stephan
S
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D014364:Tryptophan / Q000378:metabolism
D015820:Cadherins; D014364:Tryptophan