PDBsum entry 2vsd

Immune system receptor

PDB id: 2vsd

Contents

Protein chain

93 a.a. *

Ligands

NAG-NAG-BMA

Waters ×104

* Residue conservation analysis

PDB id:

2vsd

Name:

Immune system receptor

Title:

Crystal structure of chir-ab1

Structure:

Chir ab1. Chain: a. Fragment: binding-domain, residues 21-115. Engineered: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: hi 5.

Resolution:

1.82Å R-factor: 0.210 R-free: 0.247

Authors:

T.I.Arnon,J.T.Kaiser,P.J.Bjorkman

Key ref:

T.I.Arnon et al. (2008). The crystal structure of CHIR-AB1: a primordial avian classical Fc receptor. J Mol Biol, 381, 1012-1024. PubMed id: 18625238 DOI: 10.1016/j.jmb.2008.06.082

Date:

22-Apr-08 Release date: 29-Jul-08

Protein chain

Q5ZJ90  (Q5ZJ90_CHICK) -  Ig-like domain-containing protein from Gallus gallus

Seq: 218 a.a.

Struc: 93 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2008.06.082

J Mol Biol 381:1012-1024 (2008)

PubMed id: 18625238

The crystal structure of CHIR-AB1: a primordial avian classical Fc receptor.

T.I.Arnon, J.T.Kaiser, A.P.West, R.Olson, R.Diskin, B.C.Viertlboeck, T.W.Göbel, P.J.Bjorkman.

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.

Selected figure(s)

Figure 2.
Fig. 2. The dimer interface. (a) Dimerization interface region with one subunit as a surface representation (hydrophilic contact residues in light blue and hydrophobic contact residues in green) and the other subunit as transparent ribbon diagram colored as in Fig. 1b (β-strands A, B, and E are shown in blue; strands CC′FGG′ are shown in red; a 3[10] helix is shown in purple; and loops are shown in gray). Strands are labeled in white, and contact residues are shown as sticks. (b) Cross section of the dimer interface illustrating the two symmetrical intersubunit salt bridges (green lines) between Asp44 and Arg72. Water molecules (yellow spheres) that mediate a hydrogen bond network (yellow dotted line) between the Gln34 residues of each subunit are also shown. Strands are labeled in white and colored as described above. (c) Proposed orientation of a CHIR-AB1 dimer on a membrane (gray line). Monomers are colored as in Fig. 1b. The 2-fold symmetry axis relating the monomers is indicated by a vertical green dotted arrow on the plane of the page. The distance between the C-terminus of each ectodomain (45 Å) and the approximate length of the ectodomain ( vert, similar 35 Å) is indicated (black dashed lines). The eight-residue stem region connecting each ectodomain subunit to the transmembrane region is shown as a broken black bar with a maximum theoretical length of vert, similar 30 Å (calculated assuming 3.8 Å per residue). (d) Molecular surfaces of the two subunits in a CHIR-AB1 dimer, with colors highlighting the electrostatic potential calculated with APBS tools.^24 Electrostatic potential is plotted from − 11.2 kT/e (electronegative; red) to + 11.2 kT/e (electropositive; blue), with white indicating electroneutrality. The right monomer is related to the left monomer by a rotation about the indicated axis of vert, similar 170°. Black arrows point toward contact partner residues.

Figure 5.
Fig. 5. Models for the CHIR-AB1/FcY interaction. (a) Sequence alignment of the extracellular domains of CHIR-AB1 and CHIR AB2 with the D1 domains of CHIR-A2, CHIR-B2, and CHIR-AB3 (GenBank accession numbers AJ745094, AJ745095, AJ745093, AJ639837, and AJ879909, respectively). Residues at the dimer interface of CHIR-AB1 are indicated by asterisks above the sequence. (b) The ribbon diagram of a CHIR-AB1 dimer with residues that differ from CHIR-AB2 is highlighted as red (dimer interface residues) or blue (all others) sticks. The highlighted amino acids are labeled. (c) Potential models for binding between CHIR-AB1 and IgY. The CHIR-AB1 ectodomain is in blue, the ITIM in the cytoplasmic tail is represented by a rectangle, and the cell membrane is shown as a dotted black line. IgY is shown with a yellow and orange Fc region and gray Fab. Left: A dimer of CHIR-AB1 is bound asymmetrically to the lower hinge region between the C[H]2 and the C[H]3 domains of FcY, analogous to the binding of FcγRs and FcεRI to Fcs. Middle: CHIR-AB1 monomers bind to the C[H]3–C[H]4 interdomain interface to create a symmetrical 2:1 complex, analogous to the binding of FcαRI to Fc. Right: The 2-fold symmetry axis of a CHIR-AB1 dimer aligns with the 2-fold symmetry axis of FcY to form a symmetrical 2:1 complex in which each CHIR-AB1 monomer binds to the bottom of a FcY C[H]4 domain.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 381, 1012-1024) copyright 2008.

Figures were selected by an automated process.