Publications & Reports

Crystal structure of the human leukocyte Fc receptor, Fc gammaRIIa.

Maxwell KF, Powell MS, Hulett MD, Barton PA, McKenzie IF, Garrett TP, Hogarth PM
Biomolecular Research Institute, Parkville, Victoria, Australia.

Abstract

Fc gamma receptors bind IgG to initiate cellular responses against pathogens and soluble antigens. We have determined the three-dimensional structure of the extracellular portion of human Fc gammaRIIa to 2.0 A resolution providing a structural basis for the unique functions of the leukocyte FcR family. The receptor is composed of two immunoglobulin domains and arranged to expose the ligand-binding site at one end of domain 2. Using alanine mutants we find that the binding sites for IgG1 and 2 are similar but the relative importance of specific regions on the receptor varies. In crystals, Fc gammaRIIa molecules associate to resemble V(L)V(H) dimers, suggesting that two Fc gammaRIIa molecules could cooperate to bind IgG in an asymmetric manner.

Project

  • Characterising the cause of human inflammation in autoimmune disease using transgenic mouse models
    Antibodies activate and modulate normal immunity but in certain inflammatory conditions (especially autoimmunity), antibodies trigger destructive information through Fc receptors and in particular through the FcgRIIa. By blocking this receptor, destructive inflammation can be completely inhibited. This has broad implications for other related diseases including lupus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, vitiligo and vasculitis, including Wegener's granulomatosis.

Publication

  • Journal: Nature Structural Biology
  • Published: 01/05/1999
  • Volume: 6
  • Issue: 5
  • Pagination: 437-442

Author