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Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc

Herr, Andrew B. and Ballister, Edward R. and Bjorkman, Pamela J. (2003) Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc. Nature, 423 (6940). pp. 614-620. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20150401-094735599

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Abstract

Immunoglobulin-α (IgA)-bound antigens induce immune effector responses by activating the IgA-specific receptor FcαRI (CD89) on immune cells. Here we present crystal structures of human FcαRI alone and in a complex with the Fc region of IgA1 (Fcα). FcαRI has two immunoglobulin-like domains that are oriented at approximately right angles to each other. Fcα resembles the Fcs of immunoglobulins IgG and IgE, but has differently located interchain disulphide bonds and external rather than interdomain N-linked carbohydrates. Unlike 1:1 FcγRIII:IgG and FcεRI:IgE complexes, two Fc RI molecules bind each Fc dimer, one at each Cα2–Cα3 junction. The FcαRI-binding site on IgA1 overlaps the reported polymeric immunoglobulin receptor (pIgR)-binding site, which might explain why secretory IgA cannot initiate phagocytosis or bind to FcαRI-expressing cells in the absence of an integrin co-receptor.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nature01685DOIArticle
http://www.nature.com/nature/journal/v423/n6940/full/nature01685.htmlPublisherArticle
http://rdcu.be/cr3rPublisherFree ReadCube access
http://www.nature.com/nature/journal/v423/n6940/suppinfo/nature01685.htmlPublisherSupplementary Information
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2003 Nature Publishing Group. Received 26 November 2002; Accepted 7 April 2003; Published online 21 May 2003. We thank E. R. Sprague for help with data collection; E. R. Sprague, L. M. Thomas, A. P. West and K. Locher for discussions; P.M. Snow and the Caltech Protein Expression Facility for FcαRI expression; C. L. White for initial FcαRI crystallization trials; staff of the Stanford Synchrotron Radiation Laboratory for technical support; and G. Waksman, M. J. Bennett, W. L. Martin and members of the Bjorkman laboratory for comments on the manuscript. This work was supported by funds from the Damon Runyon Cancer Research Foundation (to A.B.H.), the Howard Hughes Medical Institute (to P.J.B.) and the Ralph M. Parsons Foundation for computational support.
Funders:
Funding AgencyGrant Number
Damon Runyon Cancer Research FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
Issue or Number:6940
Record Number:CaltechAUTHORS:20150401-094735599
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150401-094735599
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56273
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Apr 2015 17:10
Last Modified:03 Oct 2019 08:12

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