Mechanism of homophilic adhesion by the neural cell adhesion molecule: Use of multiple domains and flexibility Journal Article


Authors: Johnson, C. P.; Fujimoto, I.; Perrin-Tricaud, C.; Rutishauser, U.; Leckband, D.
Article Title: Mechanism of homophilic adhesion by the neural cell adhesion molecule: Use of multiple domains and flexibility
Abstract: The extracellular regions of adhesion proteins of the Ig superfamily comprise multiple, tandemly arranged domains. We used direct-force measurements to investigate how this modular architecture contributes to the adhesive interactions of the neural cell adhesion molecule (NCAM), a representative of this protein class. The extracellular region of NCAM comprises five immunoglobulin and two fibronectin domains. Previous investigations generated different models for the mechanism of homophilic adhesion that each use different domains. We use force measurements to demonstrate that NCAM binds in two spatially distinct configurations. Ig-domain deletion mutants identified the domains responsible for each of the adhesive bonds. The measurements also confirmed the existence of a flexible hinge that alters the orientation of the adhesive complexes and the intermembrane distance. These results suggest that a combination of multiple bound states and internal molecular flexibility allows for sequentially synergistic bond formation and the ability to accommodate differences in intercellular space.
Keywords: mutation; binding affinity; protein domain; electron microscopy; animals; protein protein interaction; immunoglobulin; structure activity relation; cell strain cos7; nerve cell adhesion molecule; nuclear magnetic resonance spectroscopy; protein structure, tertiary; cadherin; cell adhesion; ligand binding; lipid bilayers; lipid bilayer; deletion mutant; fibronectin; cho cell; cho cells; cricetinae; neural cell adhesion molecules; atomic force microscopy; disulfide bond; priority journal; article; interferometry
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 101
Issue: 18
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2004-05-04
Start Page: 6963
End Page: 6968
Language: English
DOI: 10.1073/pnas.0307567100
PROVIDER: scopus
PMCID: PMC406449
PUBMED: 15118102
DOI/URL:
Notes: Proc. Natl. Acad. Sci. U. S. A. -- Cited By (since 1996):39 -- Export Date: 16 June 2014 -- CODEN: PNASA -- Source: Scopus
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