Crystal Structure of a Polymeric Immunoglobulin Binding Fragment of the Human Polymeric Immunoglobulin Receptor
Abstract
The polymeric immunoglobulin receptor (pIgR) is a type I transmembrane protein that delivers dimeric IgA (dIgA) and pentameric IgM to mucosal secretions. Here, we report the 1.9 Å resolution X-ray crystal structure of the N-terminal domain of human pIgR, which binds dIgA in the absence of other pIgR domains with an equilibrium dissociation constant of 300 nM. The structure of pIgR domain 1 reveals a folding topology similar to immunoglobulin variable domains, but with differences in the counterparts of the complementarity determining regions (CDRs), including a helical turn in CDR1 and a CDR3 loop that points away from the other CDRs. The unusual CDR3 loop position prevents dimerization analogous to the pairing of antibody variable heavy and variable light domains. The pIgR domain 1 structure allows interpretation of previous mutagenesis results and structure-based comparisons between pIgR and other IgA receptors.
Additional Information
© 2004 Elsevier Ltd. Received 16 July 2004, Revised 2 September 2004, Accepted 3 September 2004, Available online 9 November 2004Published: November 9, 2004. We thank the staff at the Advanced Light Source (ALS) beamline 8.2.2 for technical support and Drs. H. Feinberg, Z.A. Hamburger and E.R. Sprague for crystallographic discussions, and Dr. Peter Snow of the Caltech Protein Expression Facility for insect cell expression of D1. We also thank Dr. A.B. Herr and members of the Bjorkman laboratory for critical reading of the manuscript. A.E.H. was supported by the Whitehead Institute for Biomedical Research and acknowledges Dr. Peter S. Kim for earlier support. A.P.W. was supported by a Career Development Award from the Burroughs-Wellcome Fund. Accession Numbers: Atomic coordinates have been deposited in the Protein Data Bank with accession code 1XED.Additional details
- Eprint ID
- 75438
- DOI
- 10.1016/j.str.2004.09.006
- Resolver ID
- CaltechAUTHORS:20170327-144357054
- Whitehead Institute for Biomedical Research
- Burroughs-Wellcome Fund
- Created
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2017-03-27Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field