Structure and transport mechanism of P5B-ATPases
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Structure and transport mechanism of P5B-ATPases
Forlagets udgivne version, 3,29 MB, PDF-dokument
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.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 3973 |
Tidsskrift | Nature Communications |
Vol/bind | 12 |
Udgave nummer | 1 |
Antal sider | 8 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2021 |
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 281708386