Alternative glycosylation modulates function of IgG and other proteins - implications on evolution and disease

Biochim Biophys Acta. 2012 Sep;1820(9):1318-26. doi: 10.1016/j.bbagen.2011.12.004. Epub 2011 Dec 13.

Abstract

Background: Nearly all membrane and secreted proteins, as well as numerous intracellular proteins are glycosylated. However, contrary to proteins which are defined by their individual genetic templates, glycans are encoded in a complex dynamic network of hundreds of genes which participate in the complex biosynthetic pathway of protein glycosylation.

Scope of review: This review summarizes present knowledge about the importance of alternative glycosylation of IgG and other proteins.

Major conclusions: Numerous proteins depend on correct glycosylation for proper function. Very good example for this is the alternative glycosylation of IgG whose effector functions can be completely changed by the addition or removal of a single monosaccharide residue from its glycans.

General significance: The change in the structure of a protein requires mutations in DNA and subsequent selection in the next generation, while even slight alterations in activity or intracellular localization of one or more biosynthetic enzymes are sufficient for the creation of novel glycan structures, which can then perform new functions. Glycome composition varies significantly between individuals, which makes them slightly or even significantly different in their ability to execute specific molecular pathways with numerous implications for development and progression of various diseases. This article is part of a Special Issue entitled Glycoproteomics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • Biosynthetic Pathways / physiology
  • Disease / etiology*
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism*
  • Glycoproteins / physiology*
  • Glycosylation
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism*
  • Immunoglobulin G / physiology*
  • Models, Biological
  • Polysaccharides / metabolism
  • Structure-Activity Relationship

Substances

  • Glycoproteins
  • Immunoglobulin G
  • Polysaccharides