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. https://resolver.caltech.edu/CaltechAUTHORS:20170327-135508111
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Abstract
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.
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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. | |||||||||
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Subject Keywords: | FcαRI; IgA1; stoichiometry; analytical ultracentrifugation; surface plasmon resonance | |||||||||
Issue or Number: | 3 | |||||||||
DOI: | 10.1016/S0022-2836(03)00149-9 | |||||||||
Record Number: | CaltechAUTHORS:20170327-135508111 | |||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20170327-135508111 | |||||||||
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, http://dx.doi.org/10.1016/S0022-2836(03)00149-9. (http://www.sciencedirect.com/science/article/pii/S0022283603001499) | |||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
ID Code: | 75427 | |||||||||
Collection: | CaltechAUTHORS | |||||||||
Deposited By: | Tony Diaz | |||||||||
Deposited On: | 27 Mar 2017 21:06 | |||||||||
Last Modified: | 15 Nov 2021 16:33 |
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