The CD58 (LFA-3) binding site is a localized and highly charged surface area on the AGFCC'C" face of the human CD2 adhesion domain.
Using site-directed mutagenesis in conjunction with NMR structural data on the adhesion domain of human CD2, we have defined the binding region for CD58. Previous structural studies of rat and human CD2 indicate that this adhesion domain is immunoglobulin-like. Here we report that the CD58 binding site is a well-circumscribed, charged surface area covering approximately 770 A2 on the AGFCC'C" face of the CD2 beta barrel. This site contains beta-strand residues in the carboxyl-terminal half of the F strand (including Lys-82 and Tyr-86), the top of the C strand (Asp-32 and Lys-34), and the C' strand (Gln-46), which are all solvent exposed. In addition, several exposed residues on the FG loop (Gly-90, Lys-91, Asn-92, and Val-93), the CC' loop (Lys-41 and Lys-43), and the C'C" loop (Arg-48 and Lys-51) form this site. In contrast, neither residues on the more peripheral G and C" strands of the same CD2 surface nor residues on B, E, and D strands of the opposite face are involved in CD58 binding. This CD58 binding site is predicted to lie most distal to the T-lymphocyte surface membrane, with ready access to CD58 on the surface of the opposing antigen-presenting cell.
Arulanandam
A R
AR
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Withka
J M
JM
Wyss
D F
DF
Wagner
G
G
Kister
A
A
Pallai
P
P
Recny
M A
MA
Reinherz
E L
EL
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001665:Binding Sites; D018801:CD2 Antigens; D018968:CD58 Antigens; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D017433:Protein Structure, Secondary; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic