Crystal structure of the complex of rat neonatal Fc receptor with Fc

Nature. 1994 Nov 24;372(6504):379-83. doi: 10.1038/372379a0.

Abstract

The neonatal Fc receptor (FcRn) transports maternal immunoglobulin G (IgG) to the bloodstream of the newborn. FcRn is structurally similar to class I major histocompatibility complex (MHC) molecules, despite differences in the ligands they bind (the Fc portion of IgG and antigenic peptides, respectively). A low-resolution crystal structure of the complex between FcRn and Fc localizes the binding site for Fc to the side of FcRn, distinct from the tops of the alpha 1 and alpha 2 domains which serve as the peptide and T-cell receptor binding sites in class I molecules. FcRn binds to Fc at the interface between the Fc CH2 and CH3 domains, which contains several histidine residues that could account for the sharply pH-dependent FcRn/IgG interaction. A dimer of FcRn heterodimers observed in the co-crystals and in the crystals of FcRn alone could be involved in binding Fc, correlating with the 2:1 binding stoichiometry between FcRn and IgG (ref. 4) and suggesting an unusual orientation of FcRn on the membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn / immunology*
  • Computer Graphics
  • Conserved Sequence
  • Crystallography, X-Ray
  • Humans
  • Immunoglobulin Fc Fragments / chemistry*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism
  • Molecular Sequence Data
  • Rats
  • Receptors, Fc / chemistry*
  • Receptors, Fc / metabolism

Substances

  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, Fc