Identification of residues in CD6 which are critical for ligand binding.
CD6 is a member of the scavenger receptor cysteine rich protein superfamily (SRCRSF). This family includes many cell surface proteins whose three-dimensional structures and functions are presently not well understood. The extracellular region of CD6 includes 3 SRCR domains. The membrane proximal SRCR domain specifically binds the activated leukocyte cell adhesion molecule (ALCAM), a CD6 ligand belonging to the immunoglobulin superfamily. CD6-ALCAM interactions mediate immune cell adhesion and are implicated in T cell maturation and the regulation of T cell function. On the basis of SRCRSF sequence comparison, a mutagenesis analysis of the membrane proximal SRCR domain of CD6 (CD6D3) has been carried out. Fifteen mutants were characterized. Three CD6 residues were identified in a region of low sequence conservation which, when mutated, abolish ligand binding but not the binding to a panel of conformationally sensitive anti-CD6 mAbs. This study provides the first analysis of residues critical for ligand binding to a member of the SRCRSF.
Bodian
D L
DL
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Skonier
J E
JE
Bowen
M A
MA
Neubauer
M
M
Siadak
A W
AW
Aruffo
A
A
Bajorath
J
J
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000595:Amino Acid Sequence / Q000235:genetics; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D020410:Activated-Leukocyte Cell Adhesion Molecule; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008024:Ligands