Emerging roles of the αC-β4 loop in protein kinase structure, function, evolution, and disease.

ABSTRACT: The faithful propagation of cellular signals in most organisms relies on the coordinated functions of a large family of protein kinases that share a conserved catalytic domain. The catalytic domain is a dynamic scaffold that undergoes large conformational changes upon activation. Most of these conformational changes, such as movement of the regulatory αC-helix from an "out" to "in" conformation, hinge on a conserved, but understudied, loop termed the αC-β4 loop, which mediates conserved interactions to tether flexible structural elements to the kinase core. We previously showed that the αC-β4 loop is a unique feature of eukaryotic protein kinases. Here, we review the emerging roles of this loop in kinase structure, function, regulation, and diseases. Through a kinome-wide analysis, we defi

SUBMITTER: Yeung W 

PROVIDER: S-EPMC8375298 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature