title: Crystal structure of prostate secretory protein PSP94 shows an edge-to-edge association of two monomers to form a homodimer.
abstract: Several recent genome-wide association studies have linked the human MSMB gene, encoding prostate secretory protein of 94 residues (PSP94), with prostate cancer susceptibility. PSP94 is one of the most abundant proteins from prostatic secretions and a primary constituent of human semen. PSP94 suppresses tumor growth and metastasis, and its expression gradually decreases during progression of the prostate cancer. It is a rapidly evolving protein with homologues present in several species with 10 conserved cysteine residues. PSP94 homologues show high-affinity binding with different proteins from the cysteine-rich secretory protein family, some of which have been shown to be ion channel blockers. Here, we report the crystal structure of human PSP94 at 2.3 A resolution. The structure shows that the amino and the carboxyl ends of the polypeptide chain are held in close proximity facing each other. A strong hydrogen bond between these ends, which are located respectively on the first and the last beta-strands, leads to formation of an almost straight edge in PSP94 structure. Crystal structure shows that these edges from two PSP94 monomers associate in antiparallel fashion, leading to formation of a dimer. Our studies further show that dimers dissociate into monomers at acidic pH, possibly through distortion of the straight edge. Further, based on several observations, we propose that PSP94 binds to cysteine-rich secretory proteins and immunoglobulin G through the same edge, which is involved in the formation of PSP94 dimeric interface.
authors.affiliation: High Pressure Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.forename: Dhanashree D
authors.initials: DD
authors.lastname: Jagtap
authors.forename: Smita D
authors.initials: SD
authors.lastname: Mahale
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029584:Prostatic Secretory Proteins / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment
chemical_list: D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein