Single-molecule Force Spectroscopy Predicts a Misfolded, Domain-swapped Conformation in human γD-Crystallin Protein.

ABSTRACT: Cataract is a protein misfolding disease where the size of the aggregate is directly related to the severity of the disorder. However, the molecular mechanisms that trigger the onset of aggregation remain unknown. Here we use a combination of protein engineering techniques and single-molecule force spectroscopy using atomic force microscopy to study the individual unfolding pathways of the human γD-crystallin, a multidomain protein that must remain correctly folded during the entire lifetime to guarantee lens transparency. When stretching individual polyproteins containing two neighboring HγD-crystallin monomers, we captured an anomalous misfolded conformation in which the β1 and β2 strands of the N terminus domain of two adjacent monomers swap. This experimentally elusive domain-swapped c

SUBMITTER: Garcia-Manyes S 

PROVIDER: S-EPMC4759196 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature