Conformational diversity of the Goodpasture antigen, the noncollagenous-1 domain of the alpha3 chain of collagen IV

Proteomics
Juan J CalveteJ Saus

Abstract

The noncollagenous-1 domain of the alpha3 chain of collagen IV networks of basement membranes is the target of an antibody-mediated inflammatory response in Goodpasture autoimmune disease. This domain when excised from basement membranes by bacterial collagenase digestion exists in two molecular forms, M(H) and M(L), that differ in cleavage site and mobility in SDS-PAGE. In the present study, M(H) and M(L) were shown to also differ with respect to epitope exposure, susceptibility to endoprotease digestion, and redox states of specific cystene residues, as determined by MS. Moreover, M(H) and M(L) assemble to form different quaternary structures, critically influencing pathogenic epitope(s) exposure and autoantibody binding. Collectively, our findings reveal that M(H) and M(L) are conformational isomers stabilized by a distinct disulfide bond connectivity, and coexist in basement membranes. The hitherto unrecognized conformational diversification of the Goodpasture autoantigen may be of relevance in pathogenesis.

References

Jul 3, 1999·Trends in Biochemical Sciences·R K Plemper, D H Wolf
Apr 24, 2002·The Journal of Biological Chemistry·Munirathinam SundaramoorthyBilly G Hudson
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Manuel E ThanWolfram Bode
Jun 20, 2003·The New England Journal of Medicine·Billy G HudsonEric G Neilson

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Citations

Jul 28, 2010·The New England Journal of Medicine·Vadim PedchenkoBilly G Hudson
Mar 8, 2011·Current Opinion in Nephrology and Hypertension·Vadim PedchenkoBilly Hudson
Mar 1, 2012·Pharmacology & Therapeutics·Janette K Burgess, Markus Weckmann
Mar 30, 2021·The Journal of Biological Chemistry·Sergei P BoudkoBilly G Hudson

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