The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex

Nature. 2000 Jul 20;406(6793):267-73. doi: 10.1038/35018508.

Abstract

The immune response depends on the binding of opsonized antigens to cellular Fc receptors and the subsequent initiation of various cellular effector functions of the immune system. Here we describe the crystal structures of a soluble Fc gamma receptor (sFc gammaRIII, CD16), an Fc fragment from human IgG1 (hFc1) and their complex. In the 1:1 complex the receptor binds to the two halves of the Fc fragment in contact with residues of the C gamma2 domains and the hinge region. Upon complex formation the angle between the two sFc gammaRIII domains increases significantly and the Fc fragment opens asymmetrically. The high degree of amino acid conservation between sFc gammaRIII and other Fc receptors, and similarly between hFc1 and related immunoglobulins, suggest similar structures and modes of association. Thus the described structure is a model for immune complex recognition and helps to explain the vastly differing affinities of other Fc gammaR-IgG complexes and the Fc epsilonRI alpha-IgE complex.

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Humans
  • Immunoglobulin Fragments / chemistry*
  • Immunoglobulin Fragments / metabolism
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / metabolism
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Receptors, IgG / chemistry*
  • Receptors, IgG / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Immunoglobulin Fragments
  • Immunoglobulin G
  • Macromolecular Substances
  • Receptors, IgG
  • Recombinant Proteins

Associated data

  • PDB/LE4J
  • PDB/LE4K