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TitleStructure and transport mechanism of P5B-ATPases.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 3973, Year 2021
Publish dateJun 25, 2021
AuthorsPing Li / Kaituo Wang / Nina Salustros / Christina Grønberg / Pontus Gourdon /
PubMed AbstractIn 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 ...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.
External linksNat Commun / PubMed:34172751 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 3.7 Å
Structure data

EMDB-13011, PDB-7op1:
Cryo-EM structure of P5B-ATPase E2PiAlF/SPM
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-13012, PDB-7op3:
Cryo-EM structure of P5B-ATPase E2PiSPM
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-13013, PDB-7op5:
Cryo-EM structure of P5B-ATPase E2P
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-13014, PDB-7op8:
Cryo-EM structure of P5B-ATPase E2Pinhibit
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

ChemComp-SPM:
SPERMINE / Spermine

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

Source
  • chaetomium thermophilum var. thermophilum dsm 1495 (fungus)
  • Chaetomium thermophilum var. thermophilum DSM 1495
  • chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (fungus)
KeywordsTRANSPORT PROTEIN / SPM transporter

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