IDENTIFICATION, SYNTHESIS AND CHARACTERIZATION OF AGGREGATION INDUCING PEPTIDES DERIVED FROM GPBP PROTEIN

摘要

Goodpasture (GP) disease is an exclusive human disorder characterized by altered renal and pulmonary functions caused by deposits of autoantibodies along the glomerular and alveolar basement membranes. The pathogenic antibodies arise against the non-collagenous C-terminal (NC1) region of the α3 chain of collagen IV (α3(IV)NC1), also called the GP antigen. The origin of the GP antigen resides in conformational changes rather than in mutations of the collagen molecules. Goodpasture antigen-binding protein (GPBP) is a non-conventional Ser/Thr protein kinase that has been cloned for its capacity to bind the N-terminal region of the human Goodpasture antigen. GPBP is highly expressed in several autoimmune conditions suggesting that its activity may be important in human autoimmune pathogenesis. GPBP interacts in vivo and in vitro with α3(IV)NCl. Interaction of GPBP with other proteins may induce conformational changes that could trigger the response of the immune system. An anomalous protein conformation could lead to protein aggregation.