Structural properties of the protein SV‐IV

Abstract

We have investigated the molecular mechanisms that produce different structural and functional behavior in the monomeric and trimeric forms of seminal vesicle protein no. 4, a protein with immunomodulatory, anti-inflammatory, and procoagulant activity secreted from the rat seminal vesicle epithelium. The monomeric and trimeric forms were characterized in solution by CD. Details of the self-association process and structural changes that accompany aggregation were investigated by different experimental approaches: trypsin proteolysis, sequence analysis, chemical modification, and computer modeling. The self-association process induces conformational change mainly in the 1-70 region, which appears to be without secondary structure in the monomer but contains a-helix in the trimer. In vivo, proteolysis of seminal vesicle protein no. 4 generates active peptides and this is affected by the monomer/trimer state, which is regulated by the concentration of the protein. The information obtained shows how conformational changes between the monomeric and trimeric forms represent a crucial aspect of activity modulation.

Anti-apoptotic seminal vesicle protein IV inhibits cell-mediated immunity

“…A peculiar feature of SV-IV is the high thermoresistance: incubation in boiling water for 30-60 min neither precipitates the protein nor changes its biological properties. The concentration of purified SV-IV was evaluated by its molar absorption at 276 nm (4100 M -1 cm -1 ) (Stiuso et al, 1999;Caporale et al, 2004).…”

“…The protein is biologically active between 2 and 30 M. Below the latter value the monomeric active population exceeds the inactive trimeric one with a maximum at about 10 M, while the opposite is true above this concentration (Stiuso et al, 1999;Caporale et al, 2004). …”

“…SV-IV gene has been isolated, sequenced, cloned, and expressed in E. coli (D'Ambrosio et al, 1993). The mature protein, purified to homogeneity, has been extensively characterized (Ostrowski et al, 1979;Pan and Li, 1982;Kandala et al, 1983;Stiuso et al, 1999;Caporale et al, 2004). SV-IV is a highly flexible molecule whose biologically active configuration is monomeric, whereas its inactive one is trimeric (Stiuso et al, 1999;Caporale et al, 2004).…”

Conformational Analysis of Rat Seminal Vesicle Secretory Protein 4, an Intrinsically Disordered Protein Having Interesting Pharmacological Properties

“…The behavior of rat RSV4 in solution has already been studied (Stiuso et al, 1999;Caporale et al, 2004) but unfortunately no information is available on its tridimensional architecture. Considering its peculiar biological function in rat fertilization as well as its interesting pharmacological properties for humans, the knowledge of RSV4 structure is a critical point because it can improve the understanding of biological function as well as be useful for drug design.…”

“…The samples were immediately used for far UV CD measurements to obtain far UV spectra best of those obtained in the past (Caporale et al, 2004) with better resolution. For this study we obtained the approval from the ethics committee at our institution (Second University of Naples).…”