title: Structural characterization of semen coagulum-derived SEM1(86-107) amyloid fibrils that enhance HIV-1 infection.
abstract: SEM1(86-107) is a 22-residue peptide corresponding to residues 86-107 in the semenogelin I protein. SEM1(86-107) is an abundant component of freshly liquefied semen and forms amyloid fibrils capable of enhancing HIV infection. To probe the factors affecting fibril formation and gain a better understanding of how differences in pH between semen and vaginal fluid affect fibril stability, this study determined the effect of pH on SEM1(86-107) fibril formation and dissociation. The SEM1(86-107) fibril structure (i.e., residues that comprise the fibrillar core) was also probed using hydrogen-deuterium exchange mass spectrometry (HDXMS) and hydroxyl radical-mediated protein modification. The average percent exposure to hydroxyl radical-mediated modification in the SEM1(86-107) fibrils was determined without requiring tandem mass spectrometry spectral acquisition or complete separation of modified peptides. It was found that the residue exposures calculated from HDXMS and hydroxyl radical-mediated modification were similar. These techniques demonstrated that three regions of SEM1(86-107) comprise the amyloid fibril core and that positively charged residues are exposed, suggesting that electrostatic interactions between SEM1(86-107) and HIV or the cell surface may be responsible for mediating HIV infection enhancement by the SEM1(86-107) fibrils.
authors.affiliation: Department of Biological Sciences and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180, United States.
authors.forename: Kinsley C
authors.initials: KC
authors.lastname: French
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Roan
authors.forename: George I
authors.initials: GI
authors.lastname: Makhatadze
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012661:Semen / Q000737:chemistry* / Q000502:physiology*; D029607:Seminal Vesicle Secretory Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D000682:Amyloid; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen