Partial magic angle spinning NMR 1H, 13C, 15N resonance assignments of the flexible regions of a monomeric alpha-synuclein: conformation of C-terminus in the lipid-bound and amyloid fibril states.
Biomol NMR Assign
; 15(2): 297-303, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-33797711
ABSTRACT
Alpha-synuclein (α-syn) is a small presynaptic protein that is believed to play an important role in the pathogenesis of Parkinson's disease (PD). It localizes to presynaptic terminals where it partitions between a cytosolic soluble and a lipid-bound state. Recent evidence suggests that α-syn can also associate with mitochondrial membranes where it interacts with a unique anionic phospholipid cardiolipin (CL). Here, we examine the conformation of the flexible fragments of a monomeric α-syn bound to lipid vesicles composed of anionic 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipids, of tetraoleoyl CL (TOCL) and DOPC, and of fibrils. The dynamic properties of α-syn associated with DOPADOPC vesicles were the most favorable for conducting three-dimensional NMR experiments, and the 13C, 15N and amide 1H chemical shifts of the flexible and disordered C-terminus of α-syn could be assigned using three-dimensional through-bond magic angle spinning NMR spectroscopy. Although the C-terminus is more dynamically constrained in fibrils and in α-syn bound to TOCLDOPC vesicles, a direct comparison of carbon chemical shifts detected using through bond two-dimensional spectroscopy indicates that the C-terminus is flexible and unstructured in all the three samples.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alfa-Sinucleína
Idioma:
En
Revista:
Biomol NMR Assign
Ano de publicação:
2021
Tipo de documento:
Article