title: 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 gamma-chain, a subunit that transmits signals upon ligation of many different immunoreceptors. Here we describe the 1.8-A-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 FcgammaRs and FcalphaRI. 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.
authors.affiliation: Division of Biology, 114-96 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Jens T
authors.initials: JT
authors.lastname: Kaiser
authors.forename: Anthony P
authors.initials: AP
authors.lastname: West
authors.forename: Rich
authors.initials: R
authors.lastname: Olson
authors.forename: Ron
authors.initials: R
authors.lastname: Diskin
authors.forename: Birgit C
authors.initials: BC
authors.lastname: Viertlboeck
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Göbel
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D015374:Biosensing Techniques; D002645:Chickens / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011961:Receptors, Fc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D030161:Avian Proteins; C016512:IgY; D007136:Immunoglobulins; D011961:Receptors, Fc