Molecular model of the N‐terminal receptor‐binding domain of the human CD6 ligand ALCAM

Abstract

CD6-ligand interactions havebeen implicated in the regulation of T-cell adhesion and activation. CD6 is a member of the scavenger receptor family, whereas its human ligand (ALCAM) belongs to the immunoglobulin superfamily. The extracellular region of ALCAM includes five immunoglobulinlike domains. As a fusion protein, the N-terminal extracellular domain of ALCAM (ALCAMDl) binds specifically to CD6. We report the construction, assessment, and analysis of a molecular model of ALCAMDl. The model defines the CDR-analogous loops, the location of N-linked glycosylation sites, and residues that form the @-sheet faces of the immunoglobulin-like domain. Predicted structural characteristics of the A'GFCC'C" face of the model are consistent with the presence of monomeric and dimeric forms of ALCAMDI, which has implications for the receptor-ligand interactions.

Mesenchymal Stem Cell Surface Antigen SB-10 Corresponds to Activated Leukocyte Cell Adhesion Molecule and Is Involved in Osteogenic Differentiation

“…Since previous data indicates that ALCAM is also capable of homophilic interactions, (23,29–31) and ALCAM expression is lost during the in vivo transition from osteoprogenitor to ALP‐positive preosteoblast, (22) we evaluated the possibility that blocking ALCAM‐mediated interactions would influence osteogenic differentiation. Preliminary studies in our laboratory also indicate that undifferentiated MSCs express low levels of CD6 on their surface.…”

Characterization of mouse ALCAM (CD166): the CD6‐binding domain is conserved in different homologs and mediates cross‐species binding

“…1). To understand better their spatial positions, these residues were mapped on a three-dimensional model of this domain in hALCAM [33] (Fig. 5) .…”

The Amino-terminal Immunoglobulin-like Domain of Activated Leukocyte Cell Adhesion Molecule Binds Specifically to the Membrane-proximal Scavenger Receptor Cysteine-rich Domain of CD6 with a 1:1 Stoichiometry

“…The chicken counterpart of ALCAM is a neural adhesion molecule capable of supporting neurite outgrowth (4,5). Data from the chicken indicate that ALCAM is capable of homophilic interactions (4,5), and the possibility of such interactions has also been suggested on the basis of molecular modeling (7). We have previously reported that COS cells that expressed CD6 were able to bind to ALCAM positive thymic epithelial cells, which suggested that CD6 and ALCAM binding can mediate adhesive interactions between thymocytes and thymic epithelial cells (2).…”