Ontology highlight
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.Methodology/principal findings
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 A?40 and HuPrP(106-140). We have found that the effects display site-specificity and vary from inhibition of fibrillation and decreased toxicity ([SeM(35)]A?40, [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/significance
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.
SUBMITTER: Martinez J
PROVIDER: S-EPMC3222675 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Martínez Javier J Lisa Silvia S Sánchez Rosa R Kowalczyk Wioleta W Zurita Esther E Teixidó Meritxell M Giralt Ernest E Andreu David D Avila Jesús J Gasset María M
PloS one 20111122 11
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>Using peptide synthesis, biophysical techniques and cell viability determinations we have studied the effect o ...[more]