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
Author
Journal
IF	>30 >20 >10 >5 all

Title	Activation and substrate specificity of the human P4-ATPase ATP8B1.
Journal, issue, pages	Nat Commun, Vol. 14, Issue 1, Page 7492, Year 2023
Publish date	Nov 18, 2023
Authors	Thibaud Dieudonné / Felix Kümmerer / Michelle Juknaviciute Laursen / Charlott Stock / Rasmus Kock Flygaard / Syma Khalid / Guillaume Lenoir / Joseph A Lyons / Kresten Lindorff-Larsen / Poul Nissen /
PubMed Abstract	Asymmetric distribution of phospholipids in eukaryotic membranes is essential for cell integrity, signaling pathways, and vesicular trafficking. P4-ATPases, also known as flippases, participate in ...Asymmetric distribution of phospholipids in eukaryotic membranes is essential for cell integrity, signaling pathways, and vesicular trafficking. P4-ATPases, also known as flippases, participate in creating and maintaining this asymmetry through active transport of phospholipids from the exoplasmic to the cytosolic leaflet. Here, we present a total of nine cryo-electron microscopy structures of the human flippase ATP8B1-CDC50A complex at 2.4 to 3.1 Å overall resolution, along with functional and computational studies, addressing the autophosphorylation steps from ATP, substrate recognition and occlusion, as well as a phosphoinositide binding site. We find that the P4-ATPase transport site is occupied by water upon phosphorylation from ATP. Additionally, we identify two different autoinhibited states, a closed and an outward-open conformation. Furthermore, we identify and characterize the PI(3,4,5)P binding site of ATP8B1 in an electropositive pocket between transmembrane segments 5, 7, 8, and 10. Our study also highlights the structural basis of a broad lipid specificity of ATP8B1 and adds phosphatidylinositol as a transport substrate for ATP8B1. We report a critical role of the sn-2 ester bond of glycerophospholipids in substrate recognition by ATP8B1 through conserved S403. These findings provide fundamental insights into ATP8B1 catalytic cycle and regulation, and substrate recognition in P4-ATPases.
External links	Nat Commun / PubMed:37980352 / PubMed Central
Methods	EM (single particle)
Resolution	2.39 - 3.4 Å
Structure data	17256 8ox4 EMDB-17256, PDB-8ox4: Cryo-EM structure of ATP8B1-CDC50A in E1-ATP conformation Method: EM (single particle) / Resolution: 3.4 Å 17257 8ox5 EMDB-17257, PDB-8ox5: Cryo-EM structure of ATP8B1-CDC50A in E1P-ADP conformation Method: EM (single particle) / Resolution: 2.9 Å 17258 8ox6 EMDB-17258, PDB-8ox6: Cryo-EM structure of ATP8B1-CDC50A in E1P conformation Method: EM (single particle) / Resolution: 2.39 Å 17259 8ox7 EMDB-17259, PDB-8ox7: Cryo-EM structure of ATP8B1-CDC50A in E2P autoinhibited "closed" conformation Method: EM (single particle) / Resolution: 2.56 Å 17260 8ox8 EMDB-17260, PDB-8ox8: Cryo-EM structure of ATP8B1-CDC50A in E2P autoinhibited "open" conformation Method: EM (single particle) / Resolution: 2.98 Å 17261 8ox9 EMDB-17261, PDB-8ox9: Cryo-EM structure of ATP8B1-CDC50A in E2P active conformation with bound PC Method: EM (single particle) / Resolution: 2.72 Å 17262 8oxa EMDB-17262, PDB-8oxa: Cryo-EM structure of ATP8B1-CDC50A in E2-Pi conformation with occluded PS Method: EM (single particle) / Resolution: 2.76 Å 17263 8oxb EMDB-17263, PDB-8oxb: Cryo-EM structure of ATP8B1-CDC50A in E2-Pi conformation with occluded PC Method: EM (single particle) / Resolution: 2.99 Å 17264 8oxc EMDB-17264, PDB-8oxc: Cryo-EM structure of ATP8B1-CDC50A in E2-Pi conformation with occluded PI Method: EM (single particle) / Resolution: 2.58 Å
Chemicals	ChemComp-ACP: PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / AMP-PCP, energy-carrying molecule analogueYM ChemComp-MG: Unknown entry ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-HOH: WATER / Water ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM / Adenosine diphosphate ChemComp-ALF: TETRAFLUOROALUMINATE ION ChemComp-IP9: (2R)-3-{[(R)-{[(1S,2S,3R,4S,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxy}(hydroxy)phosphoryl]oxy}propane ChemComp-BEF: BERYLLIUM TRIFLUORIDE ION ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM / POPC ChemComp-VN4: oxido(dioxo)vanadium ChemComp-D39: (2~{S})-2-azanyl-3-[[(2~{R})-3-hexadecanoyloxy-2-[(~{Z})-octadec-9-enoyl]oxy-propoxy]-oxidanyl-phosphoryl]oxy-propanoic acid ChemComp-PIE*: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOINOSITOL
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / lipid transporter autoinhibition P-type ATPase P4-ATPase CDC50A