Quantification of quaternary structure stability in aggregation-prone proteins under physiological conditions: the transthyretin case.

ABSTRACT: The quaternary structure stability of proteins is typically studied under conditions that accelerate their aggregation/unfolding processes on convenient laboratory time scales. Such conditions include high temperature or pressure, chaotrope-mediated unfolding, or low or high pH. These approaches have the limitation of being nonphysiological and that the concentration of the protein in solution is changing as the reactions proceed. We describe a methodology to define the quaternary structure stability of the amyloidogenic homotetrameric protein transthyretin (TTR) under physiological conditions. This methodology expands from a described approach based on the measurement of the rate of subunit exchange of TTR with a tandem flag-tagged (FT₂) TTR counterpart. We demonstrate that subunit exchan

SUBMITTER: Robinson LZ 

PROVIDER: S-EPMC4204887 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature