Conformational Ensemble Dynamics of Intrinsically Disordered Full-Length α- and β-Synuclein Monomers.

ABSTRACT: Abnormal aggregation of α-synuclein (αS) into amyloid fibrils is a hallmark of neurodegenerative diseases such as Parkinson's disease. In contrast, its homologue β-synuclein (βS), colocalized at presynaptic terminals, resists amyloid formation and can even inhibit αS fibrillization. However, how sequence variations affect their structural dynamics remains poorly understood. To address this, we conducted 100 independent 1000 ns atomistic discrete molecular dynamics simulations for both αS and βS monomers. Our results revealed that both proteins predominantly adopted intrinsically disordered conformations, punctuated by transient helices and β-sheets. Both αS and βS exhibited a conserved helical tendency in the first half of the N-terminal domain, while the latter half showed dynamic β-sheet

SUBMITTER: Lv Z 

PROVIDER: S-EPMC12455491 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature