Truncated Semenogelin I Binds Zinc and Is Cleaved by Prostate‐Specific Antigen

Abstract

Semenogelins I and II are major coagulum-forming proteins in semen, and they are secreted mainly by the seminal vesicles. These proteins bind Zn 2+ and act as substrates for prostate-specific antigen and transglutaminase. A variant semenogelin I lacking 60 amino acids has been described that occurs in different populations with an allele frequency of 1%-3%. To better understand the function of the semenogelins in vivo, our aim was to characterize the properties of the variant form and compare with the wild type. Recombinant proteins were synthesized in insect cells. Binding of Zn 2+ was studied by titration of metal ions in the presence of a zinc (II) fluorophore chelator. SDS-PAGE was used to visualize the results of cleavage by prostate-specific antigen and cross-linking with transglutaminase. We found that the truncated and wild-type semenogelin molecules had similar Zn 2+ -binding properties (ie, a stoichiometry of at least 9-10 mol per mol of protein and an average dissociation constant of 5 mmol/L per site), and they showed also similar susceptibility for degradation by prostate-specific antigen. Furthermore, like the wild-type form, the truncated semenogelin I was able to serve as a substrate for transglutaminase. These findings imply that the studied characteristics do not depend on a well-defined tertiary structure, or that the deletion has no major effect on the structure responsible for these features.

Cellular stress conditions are reflected in the protein and RNA content of endothelial cell‐derived exosomes

“…S2a). The lower band, detected in exosome sample, may represent a product of SEMG1 cleavage 42, 43, suggesting that this product is enriched in exosomes from endothelial cells grown in hypoxic conditions. The TNF‐α induced increase in TNFAIP3 was confirmed by immunoblot analysis.…”

Crystal Structure of a Ternary Complex between Human Prostate-specific Antigen, Its Substrate Acyl Intermediate and an Activating Antibody

“…Indeed, zinc inhibition is relieved by exposure to semenogelins, which are avid zinc binders, as a means to modulate PSA activity. 1,4,5 Physiological zinc inhibition is further complicated by pH variations that occur during coitus. 24 While semen is slightly alkaline (pH 7.0 to 8.0), the normal vaginal pH is 3.8 to 4.2 in healthy women.…”

“…Thus, zinc is an important modulator of PSA physiological activity. 1,4,5 Outside its physiological role, PSA as well as other kallikrein-related peptidases may participate in the process of neoplastic growth and metastasis. 6 Thus, KLK3 may influence specifically the tumoral growth of prostate cells through the degradation of insulinlike growth factor binding protein 3 and 4 to increase insulinlike growth factor bioavailability.…”

Molecular mechanism of epididymal protease inhibitor modulating the liquefaction of human semen

“…During liquefaction of semen, PSA cleaves Sg bound to the sperm surface, releasing the sperm motility inhibitory factor (amino acids 69-160) [5][6][7][8]. We now know that Sg on the sperm surface is bound to Eppin and, therefore, the cleavage of Sg by PSA must occur while Sg is bound to Eppin.…”