7OP8

Cryo-EM structure of P5B-ATPase E2Pinhibit

Summary for 7OP8

• Entry DOI: 10.2210/pdb7op8/pdb
• EMDB information: 13014
• Descriptor: Cation-transporting ATPase, BERYLLIUM TRIFLUORIDE ION, MAGNESIUM ION (3 entities in total)
• Functional Keywords: spm transporter, transport protein
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• Total number of polymer chains: 1
• Total formula weight: 156232.34

Authors

Li, P.,Gourdon, P. (deposition date: 2021-05-31, release date: 2021-06-30, Last modification date: 2024-07-17)

Primary citation

Li, P.,Wang, K.,Salustros, N.,Gronberg, C.,Gourdon, P.
Structure and transport mechanism of P5B-ATPases.
Nat Commun, 12:3973-3973, 2021

PubMed Abstract: In human cells, P5B-ATPases execute the active export of physiologically important polyamines such as spermine from lysosomes to the cytosol, a function linked to a palette of disorders. Yet, the overall shape of P5B-ATPases and the mechanisms of polyamine recognition, uptake and transport remain elusive. Here we describe a series of cryo-electron microscopy structures of a yeast homolog of human ATP13A2-5, Ypk9, determined at resolutions reaching 3.4 Å, and depicting three separate transport cycle intermediates, including spermine-bound conformations. Surprisingly, in the absence of cargo, Ypk9 rests in a phosphorylated conformation auto-inhibited by the N-terminus. Spermine uptake is accomplished through an electronegative cleft lined by transmembrane segments 2, 4 and 6. Despite the dramatically different nature of the transported cargo, these findings pinpoint shared principles of transport and regulation among the evolutionary related P4-, P5A- and P5B-ATPases. The data also provide a framework for analysis of associated maladies, such as Parkinson's disease.

PubMed: 34172751
DOI: 10.1038/s41467-021-24148-y

Experimental method

ELECTRON MICROSCOPY (3.5 Å)