Direct single-molecule observation of calcium-dependent misfolding in human neuronal calcium sensor-1.

ABSTRACT: Neurodegenerative disorders are strongly linked to protein misfolding, and crucial to their explication is a detailed understanding of the underlying structural rearrangements and pathways that govern the formation of misfolded states. Here we use single-molecule optical tweezers to monitor misfolding reactions of the human neuronal calcium sensor-1, a multispecific EF-hand protein involved in neurotransmitter release and linked to severe neurological diseases. We directly observed two misfolding trajectories leading to distinct kinetically trapped misfolded conformations. Both trajectories originate from an on-pathway intermediate state and compete with native folding in a calcium-dependent manner. The relative probability of the different trajectories could be affected by modulating the

SUBMITTER: Heidarsson PO 

PROVIDER: S-EPMC4246975 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature