The Crystal Structure of CHIR-AB1: A Primordial Avian Classical Fc Receptor
Abstract
CHIR-AB1 is a newly identified avian immunoglobulin (Ig) receptor that includes both activating and inhibitory motifs and was therefore classified as a potentially bifunctional receptor. Recently, CHIR-AB1 was shown to bind the Fc region of chicken IgY and to induce calcium mobilization via association with the common γ-chain, a subunit that transmits signals upon ligation of many different immunoreceptors. Here we describe the 1.8-Å-resolution crystal structure of the CHIR-AB1 ectodomain. The receptor ectodomain consists of a single C2-type Ig domain resembling the Ig-like domains found in mammalian Fc receptors such as FcγRs and FcαRI. Unlike these receptors and other monomeric Ig superfamily members, CHIR-AB1 crystallized as a 2-fold symmetrical homodimer that bears no resemblance to variable or constant region dimers in an antibody. Analytical ultracentrifugation demonstrated that CHIR-AB1 exists as a mixture of monomers and dimers in solution, and equilibrium gel filtration revealed a 2:1 receptor/ligand binding stoichiometry. Measurement of the 1:1 CHIR-AB1/IgY interaction affinity indicates a relatively low affinity complex, but a 2:1 CHIR-AB1/IgY interaction allows an increase in apparent affinity due to avidity effects when the receptor is tethered to a surface. Taken together, these results add to the structural understanding of Fc receptors and their functional mechanisms.
Additional Information
Copyright © 2008 Elsevier. Received 23 April 2008; received in revised form 25 June 2008; accepted 26 June 2008. Available online 3 July 2008. his work was supported by a Jane Coffin Child's Memorial Fund Fellowship for Medical Research (T.I.A.), the National Institutes of Health (2 R37 AI041239-06A1 to P.J.B.), the Beckman Institute at Caltech (R.O.), funds from the Gordon and Betty Moore Foundation in support of the Molecular Observatory at Caltech, and a Deutsche Forschungsgemeinschaft grant GO489/3-6 (T.W.G.). Atomic coordinates have been deposited in the Protein Data Bank with accession code 2VSD. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jmb.2008.06.082Attached Files
Accepted Version - nihms67904.pdf
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Additional details
- PMCID
- PMC2603183
- Eprint ID
- 11794
- Resolver ID
- CaltechAUTHORS:ARNjmb08
- Jane Coffin Childs Memorial Fund for Medical Research
- NIH
- 2 R37 AI041239-06A1
- Caltech Beckman Institute
- Gordon and Betty Moore Foundation
- Deutsche Forschungsgemeinschaft (DFG)
- GO489/3-6
- Created
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2008-09-29Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field