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Conformational diversity of the Goodpasture antigen, the noncollagenous‐1 domain of the α3 chain of collagen IV
Author(s) -
Calvete Juan J.,
Revert Fernando,
Blanco Mario,
Cervera Javier,
Tárrega Céline,
Sanz Libia,
RevertRos Francisco,
Granero Froilán,
PérezPayá Enrique,
Hudson Billy G.,
Saus Juan
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500495
Subject(s) - epitope , chemistry , basement membrane , collagenase , autoantibody , laminin , antigen , microbiology and biotechnology , biochemistry , antibody , biology , immunology , enzyme , extracellular matrix
The noncollagenous‐1 domain of the α3 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.