Molecular characteristics of the Goodpasture autoantigen

• Published in: Kidney international Vol. 43; no. 1; pp. 135 - 139
• Main Authors: Hudson, Billy G., Kalluri, Raghuram, Gunwar, Sripad, Noelken, Milton E., Mariyama, Mariko, Reeders, Stephen T.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01-01-1993; Nature Publishing
• Subjects: Amino Acid Sequence; Anti-Glomerular Basement Membrane Disease - genetics; Anti-Glomerular Basement Membrane Disease - immunology; Autoantigens - chemistry; Autoantigens - genetics; Biological and medical sciences; Collagen - chemistry; Collagen - genetics; Collagen - immunology; Epitopes - chemistry; Epitopes - genetics; Glomerulonephritis; Humans; Medical sciences; Molecular Sequence Data; Molecular Structure; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Human; Glomerulonephritis; Immunopathology; Urinary system disease; Antigenic determinant; Molecular structure; Respiratory disease; Autoimmune disease; Renal disease; Exploration; Review; Hemorrhage; Basement membrane; Antigen; Goodpasture syndrome; Collagen; Molecular biology
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1993.22

Molecular characteristics of the Goodpasture autoantigen. 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 (α3 and α4) of type IV collagen and the identification of the α3 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 α3 chain is a homotrimer. The ah-protomers associate through NC1-to-NC1 interactions mainly with each other to form a suprastructure, although some associate with protomers containing the α2(IV) and α2(IV) chains. The α3-protomers also form suprastructures involving triple helical interactions of three or more protomers. The Goodpasture epitope is localized to the carboxyl-terminal region of the α3(IV) chain, encompassing the last 36 residues of the chain, as the primary interaction site, and its structure is discontinuous.