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

Collin G. Borcik, Isaac R. Eason, Maryam Yekefallah, Reza Amani, Ruixian Han, Boden H. Vanderloop, Benjamin J. Wylie

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1 Scopus citations


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.

Original languageEnglish
Article numbere202112232
JournalAngewandte Chemie - International Edition
Issue number13
StatePublished - Mar 21 2022


  • Cholesterol
  • Inward-Rectifier K Channels
  • Membrane Proteins
  • NMR Structure
  • Solid-State NMR


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