Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection of Its Disrupting Antibodies.

TEX101 is a testis-specific protein expressed exclusively in male germ cells and is a validated biomarker of male infertility. Studies in mice suggest that TEX101 is a cell-surface chaperone which regulates, through protein-protein interactions, the maturation of proteins involved in spermatozoa transit and oocyte binding. Male TEX101-null mice are sterile. ...
Here, we identified by co-immunoprecipitation-mass spectrometry the interactome of human TEX101 in testicular tissues and spermatozoa. The testis-specific cell-surface dipeptidase 3 (DPEP3) emerged as the top hit. We further validated the TEX101-DPEP3 complex by using hybrid immunoassays. Combinations of antibodies recognizing different epitopes of TEX101 and DPEP3 facilitated development of a simple immunoassay to screen for disruptors of TEX101-DPEP3 complex. As a proof-of-a-concept, we demonstrated that anti-TEX101 antibody T4 disrupted the native TEX101-DPEP3 complex. Disrupting antibodies may be used to study the human TEX101-DPEP3 complex, and to develop modulators for male fertility.
Mesh Terms:
ADAM Proteins, Animals, Antibodies, Monoclonal, Antigens, Surface, Chromatography, Liquid, Dipeptidases, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Humans, Hybridomas, Immunoglobulin G, Infertility, Male, Male, Membrane Proteins, Mice, Mice, Inbred BALB C, Proteolysis, Spermatogenesis, Spermatozoa, Tandem Mass Spectrometry, Testis
Mol. Cell Proteomics
Date: Dec. 01, 2017
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