title: Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis and toxicity.
abstract: BACKGROUND
  The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties.
  
  
  RESULTS
  Using peptide synthesis, biophysical techniques and cell viability determinations we have studied the effect of the substitution of methionine (Met) by selenomethionine (SeM) on the fibrillogenesis and toxic properties of Aβ40 and HuPrP(106-140). We have found that the effects display site-specificity and vary from inhibition of fibrillation and decreased toxicity ([SeM(35)]Aβ40, [SeM(129)]HuPrP(106-140) and [SeM(134)]HuPrP(106-140)), retarded assembly, modulation of polymer shape and retention of toxicity ([SeM(112)]HuPrP(106-140) to absence of effects ([SeM(109)]HuPrP(106-140)).
  
  
  CONCLUSIONS
  This work provides direct evidence that the substitution of Met by SeM in proamyloid sequences has a major impact on their self-assembly and toxic properties, suggesting that the SeM pool can play a major role in dictating the allowance and efficiency of a polypeptide chain to undergo toxic polymerization.
authors: Instituto de Química-Física Rocasolano, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors: Javier
authors: J
authors: Martínez
authors: Silvia
authors: S
authors: Lisa
authors: Rosa
authors: R
authors: Sánchez
authors: Wioleta
authors: W
authors: Kowalczyk
authors: Esther
authors: E
authors: Zurita
authors: Meritxell
authors: M
authors: Teixidó
authors: Ernest
authors: E
authors: Giralt
authors: David
authors: D
authors: Andreu
authors: Jesús
authors: J
authors: Avila
authors: María
authors: M
authors: Gasset
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction / Q000187:drug effects; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D012645:Selenomethionine / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D011328:Prions; D012645:Selenomethionine