The Impairment of TorsinA's Binding to and Interactions With Its Activator: An Atomistic Molecular Dynamics Study of Primary Dystonia.

ABSTRACT: Primary dystonia's prolonged muscle contractions and the associated abnormal postures and twisting movements remain incurable. Genetic mutation/deletion of GAG from TorsonA's gene resulting in ΔE303 (which weakens the binding between TorsinA and its activator, such as LULL1) primarily cause this neurodegenerative disorder. We studied TorsinA-LULL1 (or TorsinAΔE303-LULL1) bindings and interactions. For the first time, we show the atomic details of TorsinA-LULL1 dynamic interactions and TorsinAΔE303-LULL1 dynamic interactions and their binding affinities. Our results show extensive effects of ΔE303 on TorsinAΔE303-LULL1 interactions, and suggest that the differences between TorsinA-LULL1 interactions and TorsinAΔE303-LULL1 interactions are non-subtle. ΔE303 significantly weakens TorsinAΔE303

SUBMITTER: Salawu EO 

PROVIDER: S-EPMC6048259 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature