7JHH

Cryo-EM structure of ATP-bound fully inactive AMPK in complex with Fab and nanobody

7JHH の概要

• エントリーDOI: 10.2210/pdb7jhh/pdb
• 関連するPDBエントリー: 7JHG
• EMDBエントリー: 22336 22337
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: 5'-AMP-activated protein kinase catalytic subunit alpha-1, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE MONOPHOSPHATE, ... (11 entities in total)
• 機能のキーワード: ampk, atp, fully inactive, kd-displaced, transferase-immune system complex, transferase/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 221784.02

構造登録者

Yan, Y.,Murkherjee, S.,Zhou, X.E.,Xu, T.H.,Xu, H.E.,Kossiakoff, A.A.,Melcher, K. (登録日: 2020-07-20, 公開日: 2021-07-21, 最終更新日: 2024-11-06)

主引用文献

Yan, Y.,Mukherjee, S.,Harikumar, K.G.,Strutzenberg, T.S.,Zhou, X.E.,Suino-Powell, K.,Xu, T.H.,Sheldon, R.D.,Lamp, J.,Brunzelle, J.S.,Radziwon, K.,Ellis, A.,Novick, S.J.,Vega, I.E.,Jones, R.G.,Miller, L.J.,Xu, H.E.,Griffin, P.R.,Kossiakoff, A.A.,Melcher, K.
Structure of an AMPK complex in an inactive, ATP-bound state.
Science, 373:413-419, 2021

PubMed Abstract: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates metabolism in response to the cellular energy states. Under energy stress, AMP stabilizes the active AMPK conformation, in which the kinase activation loop (AL) is protected from protein phosphatases, thus keeping the AL in its active, phosphorylated state. At low AMP:ATP (adenosine triphosphate) ratios, ATP inhibits AMPK by increasing AL dynamics and accessibility. We developed conformation-specific antibodies to trap ATP-bound AMPK in a fully inactive, dynamic state and determined its structure at 3.5-angstrom resolution using cryo-electron microscopy. A 180° rotation and 100-angstrom displacement of the kinase domain fully exposes the AL. On the basis of the structure and supporting biophysical data, we propose a multistep mechanism explaining how adenine nucleotides and pharmacological agonists modulate AMPK activity by altering AL phosphorylation and accessibility.

PubMed: 34437114
DOI: 10.1126/science.abe7565

実験手法

ELECTRON MICROSCOPY (3.92 Å)