Backbone dynamics of the first, second, and third immunoglobulin modules of the neural cell adhesion molecule (NCAM).
The neural cell adhesion molecule (NCAM) is a cell surface multimodular protein, which plays an important role in cell-cell adhesion by homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM molecules) binding. In the present study, the backbone dynamics of the first three immunoglobulin-like (Ig) modules of NCAM have been investigated by NMR spectroscopy. Ig1, Ig2, and Ig3 share low sequence identity but possess the same fold and have very similar three-dimensional structures. (15)N longitudinal and transverse relaxation rates and heteronuclear NOEs have been measured and subsequently analyzed by the axial symmetric Lipari-Szabo modelfree formalism to characterize fast (pico- to nanosecond) and slow (micro- to millisecond) motions in the three protein modules. We found that backbone motions of residues located in the beta-strand regions are generally restricted, while increased flexibility is observed in turns and loops. In all three modules, residues located in the segments connecting the C- and D-strand plus residues located in the segment connecting the E- and F-strand show significant chemical exchange on the micro- to millisecond time scale. In addition, a number of residues with small chemical exchange contribution seem to form contiguous regions in the beta sheets, suggesting that these motions might be correlated. Only few residues in the homophilic binding sites in the NCAM Ig1 and Ig2 modules show increased flexibility, indicating that the Ig1-Ig2-mediated NCAM homophilic binding does not depend on the local backbone mobility of the interacting modules.
Department of Protein Chemistry, Institute of Molecular Biology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353 Copenhagen, Denmark.
Thorsten
T
Thormann
Vladislav
V
Soroka
Steen
S
Nielbo
Vladimir
V
Berezin
Elisabeth
E
Bock
Flemming M
FM
Poulsen
D001665:Binding Sites; D002448:Cell Adhesion; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding
D007136:Immunoglobulins; D019006:Neural Cell Adhesion Molecules