Disruption of the GDNF Binding Site in NCAM DissociatesLigand Binding and Homophilic Cell Adhesion
2007 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 282, no 17, 12734-12740 p.Article in journal (Refereed) Published
Most plasma membrane proteins are capable of sensing multiple cell-cell and cell-ligand interactions, but the extent towhich this functional versatility is founded on their modular design is less clear. We have identified the third immunoglobulin domain of the Neural Cell Adhesion Molecule (NCAM) as the necessary and sufficient determinant for its interaction with Glial Cell Line-derived Neurotrophic Factor (GDNF). Four charged contacts were identified by molecular modeling as the main contributors to binding energy. Their mutation abolished GDNF binding to NCAM but left intact the ability of NCAM tomediate cell adhesion, indicating that the two functions are genetically separable. The GDNF-NCAM interface allows complex formation with the GDNF family receptor α1, shedding light on the molecular architecture of a multicomponent GDNF receptor.
Place, publisher, year, edition, pages
Bethesda, MD: American Society for Biochemistry and Molecular Biology , 2007. Vol. 282, no 17, 12734-12740 p.
homology model, protein complex, interaction interface, mutagenesis
Bioinformatics and Systems Biology
IdentifiersURN: urn:nbn:se:liu:diva-21306DOI: 10.1074/jbc.M701588200OAI: oai:DiVA.org:liu-21306DiVA: diva2:241015