Molecular characteristics of the Goodpasture autoantigen

Kidney Int. 1993 Jan;43(1):135-9. doi: 10.1038/ki.1993.22.

Abstract

Goodpasture syndrome is an autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary hemorrhage. The clinical manifestations are caused by autoantibodies that bind to a constituent, termed the Goodpasture autoantigen, of alveolar and glomerular basement membranes. Searches for the identity of this constituent have recently culminated in the discovery of two new chains (alpha 3 and alpha 4) of type IV collagen and the identification of the alpha 3 chain as the Goodpasture autoantigen. The gene, COL4A3, encoding this autoantigen was recently cloned and localized to the q35-37 region of chromosome 2. The major protomeric form of the alpha 3 chain is a homotrimer. The alpha 3-protomers associate through NC1-to-NC1 interactions mainly with each other to form a suprastructure, although some associate with protomers containing the alpha 1(IV) and alpha 2(IV) chains. The alpha 3-protomers also form suprastructures involving triple helical interactions of three or more protomers. The Goodpasture epitope is localized to the carboxylterminal region of the alpha 3(IV) chain, encompassing the last 36 residues of the chain, as the primary interaction site, and its structure is discontinuous.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anti-Glomerular Basement Membrane Disease / genetics
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Autoantigens / chemistry
  • Autoantigens / genetics*
  • Collagen / chemistry
  • Collagen / genetics
  • Collagen / immunology
  • Epitopes / chemistry
  • Epitopes / genetics
  • Humans
  • Molecular Sequence Data
  • Molecular Structure

Substances

  • Autoantigens
  • Epitopes
  • Collagen