Experimental Evidence for Phosphorylation-Driven Allosteric Regulation of Alpha Synuclein Function.

ABSTRACT: Phosphorylation of serine 129 (pS129) in the intrinsically disordered protein alpha synuclein has long been associated with neurodegenerative disease. In the past several years, the functional relevance of pS219 has been uncovered by electrophysiology, immunoprecipitation, and proteomics as intricately connected with neurotransmitter release and synaptic vesicle (SV) cycling. Unexpectedly, binding to SNARE complex proteins VAMP-2 and synapsin only occurs with phosphorylation-competent alpha synuclein. The VAMP-2 binding domain has been shown to be residues 96-110, which does not include the phosphorylated residue, hinting at allosteric regulation of alpha synuclein protein-protein interactions by pS129. Within this study, cross-linking, covalent labeling, and collision induced unfolding of

SUBMITTER: Dollar AN 

PROVIDER: S-EPMC11888164 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature