IBR 13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Conserved core of amyloid fibrils of wild type and A30P mutant alpha-synuclein
Autor/es:
MIN-KYU CHO; HAI-YOUNG KIM; CLAUDIO O. FERNANDEZ; STEFAN BECKER; MARKUS ZWECKSTETTER
Revista:
PROTEIN SCIENCE
Editorial:
JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2011 vol. 20 p. 387 - 395
ISSN:
0961-8368
Resumen:
The major component of neural inclusions that are the pathological hallmark ofParkinsons disease are amyloid fibrils of the protein alpha-synuclein (AS). Here we investigated if thedisease-related mutation A30P not only modulates the kinetics of AS aggregation, but also alters thestructure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuteriumexchange coupled to NMR spectroscopy and performed two-dimensional proton-detected highresolutionmagic angle spinning experiments. The combined data indicate that the A30P mutationdoes not cause changes in the number, location and overall arrangement of beta-strands in amyloidfibrils of AS. At the same time, several residues within the fibrillar core retain nano-second dynamics.We conclude that the increased pathogenicity related to the familial A30P mutation is unlikely to becaused by a mutation-induced change in the conformation of AS aggregates.
