Robust Sequence Determinants of α-Synuclein Toxicity in Yeast Implicate Membrane Binding.

ABSTRACT: Protein conformations are shaped by cellular environments, but how environmental changes alter the conformational landscapes of specific proteins in vivo remains largely uncharacterized, in part due to the challenge of probing protein structures in living cells. Here, we use deep mutational scanning to investigate how a toxic conformation of α-synuclein, a dynamic protein linked to Parkinson's disease, responds to perturbations of cellular proteostasis. In the context of a course for graduate students in the UCSF Integrative Program in Quantitative Biology, we screened a comprehensive library of α-synuclein missense mutants in yeast cells treated with a variety of small molecules that perturb cellular processes linked to α-synuclein biology and pathobiology. We found that the confor

SUBMITTER: Newberry RW 

PROVIDER: S-EPMC7442712 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature