56 research outputs found
Direct Observation of Defects and Increased Ion Permeability of a Membrane Induced by Structurally Disordered Cu/Zn-Superoxide Dismutase Aggregates
Interactions between protein aggregates and a cellular membrane have been strongly implicated in many protein conformational diseases. However, such interactions for the case of Cu/Zn superoxide dismutase (SOD1) protein, which is related to fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS), have not been explored yet. For the first time, we report the direct observation of defect formation and increased ion permeability of a membrane induced by SOD1 aggregates using a supported lipid bilayer and membrane patches of human embryonic kidney cells as model membranes. We observed that aggregated SOD1 significantly induced the formation of defects within lipid membranes and caused the perturbation of membrane permeability, based on surface plasmon resonance spectroscopy, atomic force microscopy and electrophysiology. In the case of apo SOD1 with an unfolded structure, we found that it bound to the lipid membrane surface and slightly perturbed membrane permeability, compared to other folded proteins (holo SOD1 and bovine serum albumin). The changes in membrane integrity and permeability were found to be strongly dependent on the type of proteins and the amount of aggregates present. We expect that the findings presented herein will advance our understanding of the pathway by which structurally disordered SOD1 aggregates exert toxicity in vivo
High-resolution structure of a type IV pilin from the metal-reducing bacterium Shewanella oneidensis
Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase.
Structural requirements of tetracycline-Tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the Tet repressor
Recommended from our members
Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase
Purification and Characterization of a p13Suc1-Bound Serine/Threonine Kinase that is Expressed in Mature Rat Brain
Synthesis and Characterization of a Monomeric Mutant Cu/Zn Superoxide Dismutase with Partially Reconstituted Enzymic Activity
- …