A Cholesterol Dimer Stabilizes the Inactivated State of an Inward-Rectifier Potassium Channel.

ABSTRACT: Cholesterol oligomers reside in multiple membrane protein X-ray crystal structures. Yet, there is no direct link between these oligomers and a biological function. Here we present the structural and functional details of a cholesterol dimer that stabilizes the inactivated state of an inward-rectifier potassium channel KirBac1.1. K⁺ efflux assays confirm that high cholesterol concentration reduces K⁺ conductance. We then determine the structure of the cholesterol-KirBac1.1 complex using Xplor-NIH simulated annealing calculations driven by solid-state NMR distance measurements. These calculations identified an α-α cholesterol dimer docked to a cleft formed by adjacent subunits of the homotetrameric protein. We compare these results to coarse grain molecular dynamics sim

SUBMITTER: Borcik CG 

PROVIDER: S-EPMC8957755 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature