8IEO

Cryo-EM structure of ATP13A2 in the nominal E1P state

Summary for 8IEO

• Entry DOI: 10.2210/pdb8ieo/pdb
• EMDB information: 35388
• Descriptor: Polyamine-transporting ATPase 13A2, TETRAFLUOROALUMINATE ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cryo-em structure of atp13a2 in the nominal e1p state; membrane protein, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 129244.60

Authors

Liu, Z.M.,Mu, J.Q.,Xue, C.Y. (deposition date: 2023-02-15, release date: 2023-12-20)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.78 Å)