title: Structural biology of NCAM homophilic binding and activation of FGFR.
abstract: In this review, we analyse the structural basis of the homophilic interactions of the neural cell adhesion molecule (NCAM) and the NCAM-mediated activation of the fibroblast growth factor receptor (FGFR). Recent structural evidence suggests that NCAM molecules form cis-dimers in the cell membrane through a high affinity interaction. These cis-dimers, in turn, mediate low affinity trans-interactions between cells via formation of either one- or two-dimensional 'zippers'. We provide evidence that FGFR is probably activated by NCAM very differently from the way by which it is activated by FGFs, reflecting the different conditions for NCAM-FGFR and FGF-FGFR interactions. The affinity of FGF for FGFR is approximately 10(6) times higher than that of NCAM for FGFR. Moreover, in the brain NCAM is constantly present on the cell surface in a concentration of about 50 microm, whereas FGFs only appear transiently in the extracellular environment and in concentrations in the nanomolar range. We discuss the structural basis for the regulation of NCAM-FGFR interactions by two molecular 'switches', polysialic acid (PSA) and adenosine triphosphate (ATP), which determine whether NCAM acts as a signalling or an adhesion molecule.
authors.affiliation: Protein Laboratory, Institute of Molecular Pathology, Panum Institute, School of Medicine, University of Copenhagen, Blegdamsvej 3C, Building 6.2, Copenhagen, Denmark.
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Kiselyov
authors.forename: Vladislav
authors.initials: V
authors.lastname: Soroka
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor