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Bivalent Binding of IgA1 to FcαRI Suggests a Mechanism for Cytokine Activation of IgA Phagocytosis

Herr, Andrew B. and White, Clinton L. and Milburn, Christina and Wu, Carol and Bjorkman, Pamela J. (2003) Bivalent Binding of IgA1 to FcαRI Suggests a Mechanism for Cytokine Activation of IgA Phagocytosis. Journal of Molecular Biology, 327 (3). pp. 645-657. ISSN 0022-2836. doi:10.1016/S0022-2836(03)00149-9.

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FcαRI, the receptor specific for the Fc region of immunoglobulin A (IgA), is responsible for IgA-mediated phagocytosis, oxidative burst, and antibody-dependent cellular cytotoxicity. Using the techniques of analytical ultracentrifugation and equilibrium gel-filtration, we show that two FcαRI molecules bind to a single Fcα homodimer. Surface plasmon resonance studies confirm the 2:1 stoichiometry of binding, with equilibrium dissociation constants of 176 nM and 431 nM for the first and second binding events, respectively. The binding affinity decreases at acidic pH in a manner consistent with protonation of a single histidine residue in the binding site. A thermodynamic analysis indicates that the histidine residue does not participate in a salt-bridge in the complex; in fact, less than 10% of the free energy of binding was contributed by electrostatic interactions. The bivalent, pH-dependent interaction between FcαRI and IgA has important implications for cytokine-dependent phagocytosis of IgA and the FcαRI-mediated degradation or recycling of IgA.

Item Type:Article
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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2003 Elsevier Science Ltd. Received 23 July 2002; received in revised form 16 January 2003; accepted 24 January 2003. We thank Anthony West, Anthony Giannetti, and Benjamin Willcox for advice on biosensor experiments; Peter Snow and Inderjit Nangiana (Caltech Protein Expression Facility) for FcαRI expression; and Michael Bradshaw and members of the Bjorkman laboratory for critical reading of the manuscript. N-terminal sequencing analysis was carried out at the Caltech Protein/Peptide Micro Analytical Laboratory (PPMAL) under the direction of Gary M. Hathaway. This work was supported by the Howard Hughes Medical Institute (to P.J.B.), and fellowships DRG-1658 (to A.B.H.) and DRG-1385 (to C.L.W.) of the Damon Runyon Cancer Research Foundation.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Damon Runyon-Walter Winchell Cancer Research FoundationDRG-1658
Damon Runyon-Walter Winchell Cancer Research FoundationDRG-1385
Subject Keywords:FcαRI; IgA1; stoichiometry; analytical ultracentrifugation; surface plasmon resonance
Issue or Number:3
Record Number:CaltechAUTHORS:20170327-135508111
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Official Citation:Andrew B Herr, Clinton L White, Christina Milburn, Carol Wu, Pamela J Bjorkman, Bivalent Binding of IgA1 to FcαRI Suggests a Mechanism for Cytokine Activation of IgA Phagocytosis, Journal of Molecular Biology, Volume 327, Issue 3, 28 March 2003, Pages 645-657, ISSN 0022-2836, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75427
Deposited By: Tony Diaz
Deposited On:27 Mar 2017 21:06
Last Modified:15 Nov 2021 16:33

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