Direct Structural Annotation of Membrane Protein Aggregation Loci using Peptide-Based Reverse Mapping.

ABSTRACT: Membrane protein aggregation is associated with neurodegenerative diseases. Despite remarkable advances to map protein aggregation, molecular elements that drive the structural transition from functional to amyloidogenic β-sheet polymers remain elusive. Here, we report a simple and reliable reverse-mapping method to identify the molecular elements. We validate our approach by obtaining molecular details of aggregation loci of human β-barrel nanopore ion channels that are vital for cell survival. By coupling bottom-up synthesis with time-resolved aggregation kinetics and high-resolution imaging, we identify molecular elements that switch folded channels to polymeric β-rich aggregates. We prove that intrinsic protein aggregation and amyloidogenicity does not depend on total hydrophobicity bu

SUBMITTER: Lella M 

PROVIDER: S-EPMC6005643 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature