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Journal of Molecular Evolution

, Volume 53, Issue 1, pp 1–9 | Cite as

Analysis of FcγRIII and IgG Fc Polymorphism Reveals Functional and Evolutionary Implications of Protein–Protein Interaction

  • Thomas D.  Kim
  • Seong-Eun  Cho
  • Chul-Hak  Yang
  • Jongsun  Kim

Abstract.

Fcγ receptor III (FcγRIII), a low-affinity receptor for the Fc portion of immunoglobulin G (IgG Fc), targets antigen-antibody complexes in a variety of effector cells of the immune system. We have investigated FcγRIII and IgG Fc polymorphism and made comparative analysis of the functional and evolutionary implications of the interaction between these two molecules. Sequence analysis and comparison of the three-dimensional structure suggest that the C-terminal Ig domain of FcγRIII is associated with the binding of IgG. The polymorphic residues of FcγRIII are mainly located in the region of the C-terminal Ig domain that might be involved in IgG binding. Therefore, polymorphism and functional binding affinity seems to be related to each other as has been increasingly implicated in clinical observations. IgG Fcs, the natural ligand of FcγRs, also exhibit significant polymorphism. Three regions have been identified where polymorphism frequently occurs: the putative FcR binding site, the linker region, and the intermolecular domain-domain interface of the second Ig domain. The putative FcγR binding sites where polymorphic, and isotype-specific residues cluster are consistent with the regions that have been identified by mutagenesis and molecular modeling studies. The polymorphic residues of IgG Fc were mainly located in the molecular surface, which could be used in the recognition of other binding molecules. These observations suggest that polymorphic and isotype-specific residues in IgG Fc are closely related to their function and protein-protein interaction. Therefore, the colocalization of the polymorphic residues of FcγRIII and IgG Fcs at their docking sites implies that the polymorphic residues would affect the IgG-FcγRIII binding interactions to optimize their signaling through evolution.

Key words: Fc receptors — Polymorphism — Protein-protein interaction — IgG Fc — Molecular evolution. 

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Copyright information

© Springer-Verlag New York Inc. 2001

Authors and Affiliations

  • Thomas D.  Kim
    • 1
  • Seong-Eun  Cho
    • 1
  • Chul-Hak  Yang
    • 2
  • Jongsun  Kim
    • 1
  1. 1.Department of Microbiology, Institute for Immunology and Immunological Diseases, College of Medicine, Yonsei University, Seoul, KoreaKR
  2. 2.School of Chemistry, College of Natural Sciences, Seoul National University, Seoul, KoreaKR

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