bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Фев. 26, 2025
Phosphorylation of serine 129 (pS129) in the intrinsically disordered protein alpha synuclein has long been associated with neurodegenerative disease. In past several years, functional relevance pS219 uncovered by electrophysiology, immunoprecipitation, and proteomics as intricately connected neurotransmitter release synaptic vesicle (SV) cycling. Unexpectedly, binding to SNARE complex proteins VAMP-2 synapsin only occurs phosphorylation-competent synuclein. The domain shown be residues 96-110, which does not include phosphorylated residue, hinting at allosteric regulation protein-protein interactions pS129. Within this study, cross-linking, covalent labeling, collision induced unfolding pS129 - well an additional encountered form brain, oxidized-M1, M5, M116, M127 are studied utilizing tandem mass spectrometry. Collision gives a fingerprint structures' relative compactness stabilities various conformations. Covalent labeling identifies solvent accessible reveals hydrophobicity (or hydrophilicity) their microenvironment, while cross-linking maps proximity residue pairs. combination unfolding, show unequivocally that phosphorylated-S129 results more stable, compact form. Our provide evidence extensively folded amphipathic region interacts strongly domain. phosphorylation-induced folding likely tunes other SVs membranes.
Язык: Английский