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Title | Structure and transport mechanism of P5B-ATPases. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 3973, Year 2021 |
Publish date | Jun 25, 2021 |
Authors | Ping Li / Kaituo Wang / Nina Salustros / Christina Grønberg / Pontus Gourdon / |
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 ...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 links | Nat Commun / PubMed:34172751 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.5 - 3.7 Å |
Structure data | EMDB-13011, PDB-7op1: EMDB-13012, PDB-7op3: EMDB-13013, PDB-7op5: EMDB-13014, PDB-7op8: |
Chemicals | ChemComp-MG: ChemComp-ALF: ChemComp-SPM: ChemComp-BEF: |
Source |
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Keywords | TRANSPORT PROTEIN / SPM transporter |