7s5t
Human KATP channel in open conformation, focused on Kir (C166S G334D double mutant) and SUR TMD0Human KATP channel in open conformation, focused on Kir (C166S G334D double mutant) and SUR TMD0
Structural highlights
Publication Abstract from PubMedKATP channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of KATP includes an inward-rectifier potassium channel (Kir) and an ABC transporter-like sulfonylurea receptor (SUR). Although structures of KATP have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic KATP (hKATP) structures with an open pore at 3.1- to 4.0-A resolution using single-particle cryo-electron microscopy (cryo-EM). Pore opening is associated with coordinated structural changes within the ATP-binding site and the channel gate in Kir. Conformational changes in SUR are also observed, resulting in an area reduction of contact surfaces between SUR and Kir. We also observe that pancreatic hKATP exhibits the unique (among inward-rectifier channels) property of PIP2-independent opening, which appears to be correlated with a docked cytoplasmic domain in the absence of PIP2. Molecular structure of an open human KATP channel.,Zhao C, MacKinnon R Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). pii: 2112267118. doi:, 10.1073/pnas.2112267118. PMID:34815345[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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