In:
Angewandte Chemie, Wiley, Vol. 134, No. 13 ( 2022-03-21)
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 simulations. This is one of the first examples of a cholesterol oligomer performing a distinct biological function and structural characterization of a conserved promiscuous lipid binding region.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.v134.13
DOI:
10.1002/ange.202112232
Language:
English
Publisher:
Wiley
Publication Date:
2022
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