Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
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Journal
IF	>30 >20 >10 >5 all

Title	Structure of an open K channel reveals tandem PIP binding sites mediating the Kir6.2 and SUR1 regulatory interface.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 2502, Year 2024
Publish date	Mar 20, 2024
Authors	Camden M Driggers / Yi-Ying Kuo / Phillip Zhu / Assmaa ElSheikh / Show-Ling Shyng /
PubMed Abstract	ATP-sensitive potassium (K) channels, composed of four pore-lining Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. K ...ATP-sensitive potassium (K) channels, composed of four pore-lining Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. K channel opening is stimulated by PIP and inhibited by ATP. Mutations that increase channel opening by PIP reduce ATP inhibition and cause neonatal diabetes. Although considerable evidence has implicated a role for PIP in K channel function, previously solved open-channel structures have lacked bound PIP, and mechanisms by which PIP regulates K channels remain unresolved. Here, we report the cryoEM structure of a K channel harboring the neonatal diabetes mutation Kir6.2-Q52R, in the open conformation, bound to amphipathic molecules consistent with natural C18:0/C20:4 long-chain PI(4,5)P at two adjacent binding sites between SUR1 and Kir6.2. The canonical PIP binding site is conserved among PIP-gated Kir channels. The non-canonical PIP binding site forms at the interface of Kir6.2 and SUR1. Functional studies demonstrate both binding sites determine channel activity. Kir6.2 pore opening is associated with a twist of the Kir6.2 cytoplasmic domain and a rotation of the N-terminal transmembrane domain of SUR1, which widens the inhibitory ATP binding pocket to disfavor ATP binding. The open conformation is particularly stabilized by the Kir6.2-Q52R residue through cation-π bonding with SUR1-W51. Together, these results uncover the cooperation between SUR1 and Kir6.2 in PIP binding and gating, explain the antagonistic regulation of K channels by PIP and ATP, and provide a putative mechanism by which Kir6.2-Q52R stabilizes an open channel to cause neonatal diabetes.
External links	Nat Commun / PubMed:38509107 / PubMed Central
Methods	EM (single particle)
Resolution	2.9 - 6.9 Å
Structure data	41277 8ti1 EMDB-41277, PDB-8ti1: Cryo-EM structure of a SUR1/Kir6.2-Q52R ATP-sensitive potassium channel in the presence of PIP2 in the open conformation Method: EM (single particle) / Resolution: 2.9 Å 41278 8ti2 EMDB-41278, PDB-8ti2: Cryo-EM structure of a SUR1/Kir6.2-Q52R ATP-sensitive potassium channel in the presence of PIP2 in the open conformation Method: EM (single particle) / Resolution: 3.28 Å EMDB-43766: Kir6.2-Q52R/SUR1 apo closed channel Method: EM (single particle) / Resolution: 6.9 Å
Chemicals	ChemComp-PT5: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho / phospholipidYM / Phosphatidylinositol 4,5-bisphosphate ChemComp-K: Unknown entry ChemComp-PEF: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / phospholipidYM / Phosphatidylethanolamine ChemComp-P5S: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine / Phosphatidylserine ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-HOH: WATER / Water
Source	rattus norvegicus (Norway rat) mesocricetus auratus (golden hamster)
Keywords	TRANSPORT PROTEIN / ATP-sensitive potassium channel / KATP channel / SUR1 / Kir6.2-Q52R / potassium transport / metabolic sensor / diabetes / phospholipid binding / PIP2