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
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
PubMed ID: 30097533
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