Mapping the conformational energy landscape of Abl kinase using ClyA nanopore tweezers.

ABSTRACT: Protein kinases play central roles in cellular regulation by catalyzing the phosphorylation of target proteins. Kinases have inherent structural flexibility allowing them to switch between active and inactive states. Quantitative characterization of kinase conformational dynamics is challenging. Here, we use nanopore tweezers to assess the conformational dynamics of Abl kinase domain, which is shown to interconvert between two major conformational states where one conformation comprises three sub-states. Analysis of kinase-substrate and kinase-inhibitor interactions uncovers the functional roles of relevant states and enables the elucidation of the mechanism underlying the catalytic deficiency of an inactive Abl mutant G321V. Furthermore, we obtain the energy landscape of Abl kinase by qua

SUBMITTER: Li F 

PROVIDER: S-EPMC9209526 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature