7FJP

Cryo EM structure of lysosomal ATPase

7FJP の概要

• エントリーDOI: 10.2210/pdb7fjp/pdb
• EMDBエントリー: 31626
• 分子名称: Polyamine-transporting ATPase 13A2, PHOSPHATE ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: lysosomal atpase transporter, 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: 125810.63

構造登録者

Zhang, S.S. (登録日: 2021-08-04, 公開日: 2023-03-08)

主引用文献

Chen, X.,Zhou, M.,Zhang, S.,Yin, J.,Zhang, P.,Xuan, X.,Wang, P.,Liu, Z.,Zhou, B.,Yang, M.
Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2.
Cell Discov, 7:106-106, 2021

PubMed Abstract: Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.

PubMed: 34728622
DOI: 10.1038/s41421-021-00334-6

実験手法

ELECTRON MICROSCOPY (3 Å)