Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28.
The structure of human CTLA-4 reveals that residues Met 99, Tyr 100 and Tyr 104 of the M99YPPPY104 motif are adjacent to a patch of charged surface residues on the A'GFCC' face of the protein. Mutation of these residues, which are conserved in the CTLA-4/CD28 family, significantly reduces binding to CD80 and/or CD86, implicating this patch as a ligand binding site.
Metzler
W J
WJ
Bajorath
J
J
Fenderson
W
W
Shaw
S Y
SY
Constantine
K L
KL
Naemura
J
J
Leytze
G
G
Peach
R J
RJ
Lavoie
T B
TB
Mueller
L
L
Linsley
P S
PS
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D001665:Binding Sites; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D017124:Conserved Sequence; D019281:Dimerization; D006801:Humans; D018796:Immunoconjugates; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013440:Sulfides
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D012996:Solutions; D013440:Sulfides; D000069594:Abatacept