Structural basis for the activation of FGFR by NCAM.
The fibroblast growth factor receptor (FGFR) can be activated through direct interaction with the neural cell adhesion molecule (NCAM). The extracellular part of the FGFR consists of three immunoglobulin-like (Ig) modules, and that of the NCAM consists of five Ig and two fibronectin type III (F3) modules. NCAM-FGFR interactions are mediated by the third FGFR Ig module and the second NCAM F3 module. Using surface plasmon resonance and nuclear magnetic resonance analyses, the present study demonstrates that the second Ig module of FGFR also is involved in binding to the NCAM. The second Ig module residues involved in binding were identified and shown to be localized on the "opposite sides" of the module, indicating that when NCAMs are clustered (e.g., due to homophilic binding), high-affinity FGFR binding sites may be formed by the neighboring NCAMs.
Kochoyan
Arthur
A
Protein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Arthur@sund.ku.dk
Poulsen
Flemming M
FM
Berezin
Vladimir
V
Bock
Elisabeth
E
Kiselyov
Vladislav V
VV
D000818:Animals; D001665:Binding Sites; D051379:Mice; D008958:Models, Molecular; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000819:agonists / Q000737:chemistry
D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins