title: How do amino acid substitutions affect the amyloidogenic properties and seeding efficiency of prion peptides.
abstract: The amino acid sequences in the amyloidogenic region (amino acids 108-144) of several mammalian prion proteins were compared and variations were found to occur at residues 109 (M or L), 112 (M or V), 129 (M, V, or L), 135 (N or S), 138 (M, L, or I), 139 (M or I), and 143 (N or S). Using the bovine PrP peptide (residues 108-144 based on the numbering of the human prion protein sequence) as a control peptide, several peptides with one amino acid differing from that of the bovine PrP peptide at residues 109, 112, 135, 138, 139, or 143 and several mammalian PrP peptides were synthesized, and the effects of these amino acid substitutions on the amyloidogenic properties of these peptides were compared and discussed on the basis of the chemical and structural properties of amino acids. Our results showed that the V112M substitution accelerated nucleation of amyloidogenesis, while the N143S and I139M substitutions retarded nucleation. These effects tended to cancel each other out when two substitutions with opposite effects were present on the same peptide. Moreover, acceleration or inhibition of nucleation was not necessarily correlated with effect on seeding efficiency. Using amyloid fibrils prepared from the bovine PrP peptide as seeds, the seeding efficiency for the monomer peptides with the M129L, S135N, N143S, or I139M substitution was decreased compared to that for bPrP peptide. Of all the mammalian peptides used in this study, the dog, mule deer, and pig PrP peptides had the lowest seeding efficiencies.
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei, 106, Taiwan, ROC.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Chuang
authors.forename: Tai-Yan
authors.initials: TY
authors.lastname: Liao
authors.forename: Eric H-L
authors.initials: EH
authors.lastname: Chen
authors.forename: Rita P-Y
authors.initials: RP
authors.lastname: Chen
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D058227:Amyloidogenic Proteins / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D003670:Deer; D004285:Dogs; D006801:Humans; D011328:Prions / Q000737:chemistry*; D013552:Swine
chemical_list: D000596:Amino Acids; D058227:Amyloidogenic Proteins; D011328:Prions