title: Micro-heterogeneity of human saliva Peptide P-C characterized by high-resolution top-down Fourier-transform mass spectrometry.
abstract: Top-down proteomics characterizes protein primary structures with unprejudiced descriptions of expressed and processed gene products. Gene sequence polymorphisms, protein post-translational modifications, and gene sequence errors can all be identified using top-down proteomics. Saliva offers advantages for proteomic research because of availability and the noninvasiveness of collection and, for these reasons, is being used to search for disease biomarkers. The description of natural protein variants, and intra- and inter-individual polymorphisms, is necessary for a complete description of any proteome, and essential for the discovery of disease biomarkers. Here, we report a striking example of natural protein variants with the discovery by top-down proteomics of two new variants of Peptide P-C. Intact mass measurements, and collisionally activated-, infrared multiphoton-, and electron capture-dissociation, were used for characterization of the form predicted from the gene sequence with an average mass 4371 Da, a form postulated to result from a single nucleotide polymorphism of mass 4372 Da, and another form of mass 4370 Da postulated to arise from a novel protein sequence polymorphism. While the biological significance of such subtle variations in protein structure remains unclear, their importance cannot be assigned without their characterization, as is reported here for one of the major salivary proteins.
authors.affiliation: The Pasarow Mass Spectrometry Laboratory, NPI-Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. fhalgand@ifr88.cnrs-mrs.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Halgand
authors.forename: Vlad
authors.initials: V
authors.lastname: Zabrouskov
authors.forename: Sara
authors.initials: S
authors.lastname: Bassilian
authors.forename: Puneet
authors.initials: P
authors.lastname: Souda
authors.forename: David T
authors.initials: DT
authors.lastname: Wong
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.forename: Julian P
authors.initials: JP
authors.lastname: Whitelegge
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005583:Fourier Analysis; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods*; D011110:Polymorphism, Genetic; D040901:Proteomics / Q000379:methods*; D055273:Salivary Proline-Rich Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: C524536:PRH1 protein, human; D055273:Salivary Proline-Rich Proteins