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	Structural insights into GIRK2 channel modulation by cholesterol and PIP.
Journal, issue, pages	Cell Rep, Vol. 36, Issue 8, Page 109619, Year 2021
Publish date	Aug 24, 2021
Authors	Yamuna Kalyani Mathiharan / Ian W Glaaser / Yulin Zhao / Michael J Robertson / Georgios Skiniotis / Paul A Slesinger /
PubMed Abstract	G-protein-gated inwardly rectifying potassium (GIRK) channels are important for determining neuronal excitability. In addition to G proteins, GIRK channels are potentiated by membrane cholesterol, ...G-protein-gated inwardly rectifying potassium (GIRK) channels are important for determining neuronal excitability. In addition to G proteins, GIRK channels are potentiated by membrane cholesterol, which is elevated in the brains of people with neurodegenerative diseases such as Alzheimer's dementia and Parkinson's disease. The structural mechanism of cholesterol modulation of GIRK channels is not well understood. In this study, we present cryo- electron microscopy (cryoEM) structures of GIRK2 in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS) and phosphatidylinositol 4,5-bisphosphate (PIP). The structures reveal that CHS binds near PIP in lipid-facing hydrophobic pockets of the transmembrane domain. Our structural analysis suggests that CHS stabilizes PIP interaction with the channel and promotes engagement of the cytoplasmic domain onto the transmembrane region. Mutagenesis of one of the CHS binding pockets eliminates cholesterol-dependent potentiation of GIRK2. Elucidating the structural mechanisms underlying cholesterol modulation of GIRK2 channels could facilitate the development of therapeutics for treating neurological diseases. VIDEO ABSTRACT.
External links	Cell Rep / PubMed:34433062 / PubMed Central
Methods	EM (single particle)
Resolution	3.2 - 7.7 Å
Structure data	22150 6xeu EMDB-22150, PDB-6xeu: CryoEM structure of GIRK2PIP2* - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 Method: EM (single particle) / Resolution: 3.2 Å EMDB-22151: CryoEM structure of GIRK2-PIP2 - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 Method: EM (single particle) / Resolution: 4.8 Å EMDB-22152: CryoEM structure of GIRK2-PIP2* - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 Method: EM (single particle) / Resolution: 7.7 Å EMDB-22153: CryoEM structure of GIRK2-PIP2** - G protein-gated inwardly rectifying potassium channel GIRK2 with PIP2 Method: EM (single particle) / Resolution: 7.7 Å 22154 6xev EMDB-22154, PDB-6xev: CryoEM structure of GIRK2-PIP2/CHS - G protein-gated inwardly rectifying potassium channel GIRK2 with modulators cholesteryl hemisuccinate and PIP2 Method: EM (single particle) / Resolution: 3.5 Å EMDB-22155: CryoEM structure of apo G protein-gated inwardly rectifying potassium channel GIRK2 Method: EM (single particle) / Resolution**: 4.8 Å
Chemicals	ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate ChemComp-K: Unknown entry ChemComp-NA: Unknown entry ChemComp-Y01: CHOLESTEROL HEMISUCCINATE
Source	mus musculus (house mouse)
Keywords	TRANSPORT PROTEIN / GIRK / inwardly rectifying potassium channel / cholesterol / lipids / PIP2 / CryoEM