PDBsum entry 1ovz

Immune system

PDB id: 1ovz

Contents

Protein chains

193 a.a. *

181 a.a. *

Ligands

NAG-NAG

NAG ×3

TRS

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Insights into iga-Mediated immune responses from the crystal structures of human fcalphari and its complex with iga1-Fc.

Authors

A.B.Herr, E.R.Ballister, P.J.Bjorkman.

Ref.

Nature, 2003, 423, 614-620. [DOI no: 10.1038/nature01685]

PubMed id

12768205

Abstract

Immunoglobulin-alpha (IgA)-bound antigens induce immune effector responses by activating the IgA-specific receptor FcalphaRI (CD89) on immune cells. Here we present crystal structures of human FcalphaRI alone and in a complex with the Fc region of IgA1 (Fcalpha). FcalphaRI has two immunoglobulin-like domains that are oriented at approximately right angles to each other. Fcalpha 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 FcgammaRIII:IgG and Fc epsilon RI:IgE complexes, two FcalphaRI molecules bind each Fcalpha dimer, one at each Calpha2-Calpha3 junction. The FcalphaRI-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 FcalphaRI-expressing cells in the absence of an integrin co-receptor.

Figure 2.
Figure 2: Fc alpha-structure. a, Ribbon diagrams showing front (left) and side (right) views of Fc (top) and Fc (bottom)33. Disulphide bonds are shown in yellow and carbohydrate residues are shown in ball-and-stick representation. b, Topology diagram of Fc . -Strands are blue or magenta, 3[10] and -helices are light blue and disulphides are yellow. The proposed C241 -C241 disulphide bond (not present in our construct) is shown as a dashed yellow line. Blue and magenta dots show residues that contact Fc RI.

Figure 4.
Figure 4: Fc alpha-RI:Fc alpha-interface. Stereoviews of residues at the Fc RI:Fc interface (defined as residues with any non-hydrogen atom within 4 Å of the partner domain). Potential hydrogen bonds are shown as black dotted lines. Residues are colour-coded according to protein (a), the chemical character of their side chains (b), or their effects on binding affinity when substituted^13,14,26 -28 (c).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 423, 614-620) copyright 2003.

Secondary reference #1

Title

Bivalent binding of iga1 to fcalphari suggests a mechanism for cytokine activation of iga phagocytosis.

Authors

A.B.Herr, C.L.White, C.Milburn, C.Wu, P.J.Bjorkman.

Ref.

J Mol Biol, 2003, 327, 645-657. [DOI no: 10.1016/S0022-2836(03)00149-9]

PubMed id

12634059

Figure 1.
Figure 1. Analytical ultracentrifugation of FcaRI and Fca. (a) and (b) Sedimentation equilibrium analyses of FcaRI (a) and Fca (b) at four speeds. The data were globally fit to a single-species model, with residuals shown in each top panel. (c) and (d) Sedimentation velocity analyses of FcaRI (c) and Fca (d). The data were fit to a modified form of the Lamm equation[45.] describing sedimentation of a single species.

Figure 2.
Figure 2. Stoichiometry of the FcaRI:Fca interaction. (a) Equilibrium gel-filtration of FcaRI:Fca mixtures. Mixtures of FcaRI and Fca were injected onto a column pre-equilibrated with 1 µM Fca. (b) Sedimentation velocity of FcaRI:Fca mixtures. The differential sedimentation coefficient distribution was determined for FcaRI and Fca alone, and for mixtures containing 1:1, 2:1, 4:1, and 6:1 molar ratios of FcaRI:Fca. The arrows identify the peaks corresponding to free FcaRI, free Fca, and 1:1 and 2:1 FcaRI:Fca complexes with their calculated molecular masses. Peak heights were normalized.

The above figures are reproduced from the cited reference with permission from Elsevier