7VPL

Cryo-EM structure of the human ATP13A2 (SPM-bound E2Pi state)

7VPL の概要

• エントリーDOI: 10.2210/pdb7vpl/pdb
• EMDBエントリー: 32069
• 分子名称: Polyamine-transporting ATPase 13A2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: atp13a2, park9, p-type atpase, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 130067.41

構造登録者

Tomita, A.,Yamashita, K.,Nishizawa, T.,Nureki, O. (登録日: 2021-10-17, 公開日: 2021-12-29, 最終更新日: 2024-11-06)

主引用文献

Tomita, A.,Daiho, T.,Kusakizako, T.,Yamashita, K.,Ogasawara, S.,Murata, T.,Nishizawa, T.,Nureki, O.
Cryo-EM reveals mechanistic insights into lipid-facilitated polyamine export by human ATP13A2.
Mol.Cell, 81:4799-4809.e5, 2021

PubMed Abstract: The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine exporter responsible for polyamine release into the cytosol, and its dysfunction is associated with Alzheimer's disease and other neural degradation diseases. ATP13A2 belongs to the P5 subfamily of the P-type ATPase family, but its mechanisms remain unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ATP13A2 under four different conditions, revealing the structural coupling between the polyamine binding and the dephosphorylation. Polyamine is bound at the luminal tunnel and recognized through numerous electrostatic and π-cation interactions, explaining its broad specificity. The unique N-terminal domain is anchored to the lipid membrane to stabilize the E2P conformation, thereby accelerating the E1P-to-E2P transition. These findings reveal the distinct mechanism of P5B ATPases, thereby paving the way for neuroprotective therapy by activating ATP13A2.

PubMed: 34798056
DOI: 10.1016/j.molcel.2021.11.001

実験手法

ELECTRON MICROSCOPY (3.78 Å)