Limited role of charge matching in the interaction of human immunoglobulin A with the immunoglobulin A Fc receptor (Fc alpha RI) CD89.
Human immunoglobulin A (IgA) mediates protective effector mechanisms through interaction with specific cellular Fc receptors (Fc alpha RI). Two IgA Fc interdomain loops (Leu257-Leu258 in the CH2 domain and Pro440-Phe443 in the CH3 domain) have previously been identified as critical for binding to Fc alpha RI. On the receptor, the interaction site for IgA has been localized to the EC1 domain. The essential Fc alpha RI residues involved are Tyr35, Tyr81 and Arg82, with contributions also from Arg52 and to a lesser extent from His85 and Tyr86. The basic nature of the side chains of some of the receptor residues implicated in ligand binding suggested that charge matching might play some role in the interaction. To address this possibility, we have generated five IgA1 mutants with point substitutions in acidic residues lying close to the putative interaction site and assessed their abilities to bind Fc alpha RI on human neutrophils. Mutants E254A, E254L and E437A displayed affinities for Fc alpha RI comparable to that of wild-type IgA1, while mutants D255A and D255V had only slightly reduced affinities for the receptor. Therefore, electrostatic interactions appear unlikely to play a significant role in the IgA-Fc alpha RI interaction. Moreover, the lack of effect of mutations in residues adjacent to those previously implicated in binding, reaffirms the importance of the interdomain loops in Fc alpha RI binding.
Pleass
Richard J
RJ
Department of Molecular and Cellular Pathology, University of Dundee Medical School, Dundee, UK.
Dehal
Prabhjyot K
PK
Lewis
Melanie J
MJ
Woof
Jenny M
JM
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D009504:Neutrophils / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011961:Receptors, Fc / Q000737:chemistry / Q000378:metabolism*; D055672:Static Electricity
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc