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8OX4

Cryo-EM structure of ATP8B1-CDC50A in E1-ATP conformation

8OX4 の概要
エントリーDOI10.2210/pdb8ox4/pdb
EMDBエントリー17256
分子名称Phospholipid-transporting ATPase IC, Cell cycle control protein 50A, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
機能のキーワードlipid transporter autoinhibition p-type atpase p4-atpase cdc50a, membrane protein
由来する生物種Homo sapiens (human)
詳細
タンパク質・核酸の鎖数2
化学式量合計178927.92
構造登録者
主引用文献Dieudonne, T.,Kummerer, F.,Laursen, M.J.,Stock, C.,Flygaard, R.K.,Khalid, S.,Lenoir, G.,Lyons, J.A.,Lindorff-Larsen, K.,Nissen, P.
Activation and substrate specificity of the human P4-ATPase ATP8B1.
Nat Commun, 14:7492-7492, 2023
Cited by
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 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.
PubMed: 37980352
DOI: 10.1038/s41467-023-42828-9
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (3.4 Å)
構造検証レポート
Validation report summary of 8ox4
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-11-06に公開中

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