EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Activation and substrate specificity of the human P4-ATPase ATP8B1.
ジャーナル・号・ページ	Nat Commun, Vol. 14, Issue 1, Page 7492, Year 2023
掲載日	2023年11月18日
著者	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 要旨	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.
リンク	Nat Commun / PubMed:37980352 / PubMed Central
手法	EM (単粒子)
解像度	2.39 - 3.4 Å
構造データ	17256 8ox4 EMDB-17256, PDB-8ox4: Cryo-EM structure of ATP8B1-CDC50A in E1-ATP conformation 手法: EM (単粒子) / 解像度: 3.4 Å 17257 8ox5 EMDB-17257, PDB-8ox5: Cryo-EM structure of ATP8B1-CDC50A in E1P-ADP conformation 手法: EM (単粒子) / 解像度: 2.9 Å 17258 8ox6 EMDB-17258, PDB-8ox6: Cryo-EM structure of ATP8B1-CDC50A in E1P conformation 手法: EM (単粒子) / 解像度: 2.39 Å 17259 8ox7 EMDB-17259, PDB-8ox7: Cryo-EM structure of ATP8B1-CDC50A in E2P autoinhibited "closed" conformation 手法: EM (単粒子) / 解像度: 2.56 Å 17260 8ox8 EMDB-17260, PDB-8ox8: Cryo-EM structure of ATP8B1-CDC50A in E2P autoinhibited "open" conformation 手法: EM (単粒子) / 解像度: 2.98 Å 17261 8ox9 EMDB-17261, PDB-8ox9: Cryo-EM structure of ATP8B1-CDC50A in E2P active conformation with bound PC 手法: EM (単粒子) / 解像度: 2.72 Å 17262 8oxa EMDB-17262, PDB-8oxa: Cryo-EM structure of ATP8B1-CDC50A in E2-Pi conformation with occluded PS 手法: EM (単粒子) / 解像度: 2.76 Å 17263 8oxb EMDB-17263, PDB-8oxb: Cryo-EM structure of ATP8B1-CDC50A in E2-Pi conformation with occluded PC 手法: EM (単粒子) / 解像度: 2.99 Å 17264 8oxc EMDB-17264, PDB-8oxc: Cryo-EM structure of ATP8B1-CDC50A in E2-Pi conformation with occluded PI 手法: EM (単粒子) / 解像度: 2.58 Å
化合物	ChemComp-ACP: PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / β,γ-メチレンATP / AMP-PCP, エネルギー貯蔵分子類似体YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-HOH: WATER / 水 ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM / アデノシン二リン酸 ChemComp-ALF: TETRAFLUOROALUMINATE ION / テトラフルオロアルミナ-ト 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 / 1-O-(1-O,2-O-ジオクタノイル-L-グリセロ-3-ホスホ)-D-myo-イノシト-ル3,4,5-トリスりん酸 ChemComp-BEF: BERYLLIUM TRIFLUORIDE ION ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM / POホスファチジルコリン 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 / 1-パルミトイル-2-オレオイルホスファチジルセリン ChemComp-PIE*: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOINOSITOL
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / lipid transporter autoinhibition P-type ATPase P4-ATPase CDC50A