Anti-idiotypic monoclonal antibody recognizes a consensus recognition site for phosphatidylserine in phosphatidylserine-specific monoclonal antibody and protein kinase C.
In order to elucidate the molecular mechanisms responsible for the specific lipid-protein interactions, we have undertaken structural and idiotypic analyses of a monoclonal antibody, PS4A7, which binds specifically to phosphatidylserine (PS). Here we showed that one of the anti-idiotypic monoclonal antibodies raised against PS4A7 cross-reacted extensively with protein kinase C (PKC) and inhibited the activation of the enzymatic activity. The binding of the anti-idiotypic antibody to PKC was inhibited specifically by PS, but not by other phospholipids including 1,2-diacyl-sn-glycero-3-phospho-D-serine or 1,2-diacyl-sn-glycero-3-phospho-L-homoserine. In contrast, the binding of the anti-idiotypic mAb to the enzyme was significantly enhanced in the presence of either diacylglycerol or sphingosine. These findings indicate that the PS-specific monoclonal antibody and PKC share a consensus structure which is responsible for the specific interaction with PS and both diacylglycerol and sphingosine may induce a similar conformational change which exposes the PS-specific binding site of the enzyme.
Reza
F
F
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Igarashi
K
K
Tokita
S
S
Asai
K
K
Aoki
J
J
Asaoka
Y
Y
Umeda
M
M
Inoue
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D004075:Diglycerides / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006433:Hemocyanins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D013110:Sphingosine / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D004075:Diglycerides; D010718:Phosphatidylserines; D006433:Hemocyanins; D011493:Protein Kinase C; C032808:keyhole-limpet hemocyanin; D013110:Sphingosine; C013965:diolein