8IEO

Cryo-EM structure of ATP13A2 in the nominal E1P state

8IEO の概要

• エントリーDOI: 10.2210/pdb8ieo/pdb
• EMDBエントリー: 35388
• 分子名称: Polyamine-transporting ATPase 13A2, TETRAFLUOROALUMINATE ION, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: cryo-em structure of atp13a2 in the nominal e1p state; membrane protein, transport 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: 129244.60

構造登録者

Liu, Z.M.,Mu, J.Q.,Xue, C.Y. (登録日: 2023-02-15, 公開日: 2023-12-20)

主引用文献

Mu, J.,Xue, C.,Fu, L.,Yu, Z.,Nie, M.,Wu, M.,Chen, X.,Liu, K.,Bu, R.,Huang, Y.,Yang, B.,Han, J.,Jiang, Q.,Chan, K.C.,Zhou, R.,Li, H.,Huang, A.,Wang, Y.,Liu, Z.
Conformational cycle of human polyamine transporter ATP13A2.
Nat Commun, 14:1978-1978, 2023

PubMed Abstract: Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson's disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases.

PubMed: 37031211
DOI: 10.1038/s41467-023-37741-0

実験手法

ELECTRON MICROSCOPY (3.78 Å)