Novel partners of SPAG11B isoform D in the human male reproductive tract.

Human sperm-associated antigen 11 is closely related to beta-defensins in structure, expression, and function. Like the beta-defensins, proteins are predominantly expressed in the male reproductive tract, where their best-known major roles are in innate host defense and reproduction. Although several hypotheses have emerged to describe the evolution of beta-defensin and duanyu1842G11 multifunctionality, few describe these multiple functions in terms of defensin interactions with specific proteins. To gain insight into the protein interaction potentials of duanyu1842G11 and the signaling pathways that duanyu1842G11 may influence, we used a yeast two-hybrid screening of a human testis-epididymis library. The results reveal human isoform D interactions with tryptase alpha/beta 1 (TPSAB1), tetraspanin 7 and attractin (ATRN). These interactions were confirmed by coimmunoprecipitation and glutathione S-transferase affinity matrix binding. and the three interacting proteins are expressed in the proximal epididymis, and all function in immunity and fertility pathways. We analyzed the functional consequences of duanyu1842G11B/D interaction with TPSAB1 and showed that duanyu1842G11B/D is both a substrate and a potent inhibitor of TPSAB1 activity. Furthermore, we show that (like and ATRN are associated with spermatozoa.

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