Molecular modelling of the immunoglobulin-like domains of the neural cell adhesion molecule (NCAM): implications for the positioning of functionally important sugar side chains.
The neural cell adhesion molecule (NCAM) is thought to mediate cell-cell adhesion by a homophilic mechanism involving binding sites located in the N-terminal region of the protein. This region of the molecule consists of five domains that are homologous to each other and share conserved residues with immunoglobulin domains. We report here secondary structure predictions for the five NCAM domains and three-dimensional models for two of them. The results are entirely consistent with an immunoglobulin-like folding of the NCAM domains into seven strands forming two beta-sheets. NCAM-NCAM binding may thus be analogous to the pairwise associations of immunoglobulin constant domains, which are involved in dimer formation. Insertions and deletions are located mostly in beta-turn regions. Two alpha-helical regions in the third and fourth domain are predicted with high probability. NCAM bears two kinds of functionally important sugar side chains, sialic acid polymers in the fifth domain, which modulate NCAM binding, and the L2 moiety, which is involved in cell adhesion and can be assigned to the third domain. Three-dimensional modelling of the corresponding domains indicates that two of the three sites for N-linked glycosylation in the fifth and the single site in the third domain are located on the face of the domain, which in immunoglobulin constant regions engages in intermolecular interactions.
Santoni
M J
MJ
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Goridis
C
C
Fontecilla-Camps
J C
JC
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000276:immunology*; D002241:Carbohydrates / Q000032:analysis*; D015815:Cell Adhesion Molecules; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data
D000954:Antigens, Surface; D002241:Carbohydrates; D015815:Cell Adhesion Molecules