HIV-tat protein forms phosphoinositide-dependent membrane pores implicated in unconventional protein secretion

HIV-Tat has been demonstrated to be secreted from cells in a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-dependent manner. Here we show that HIV-Tat forms membrane-inserted oligomers, a process that is accompanied by changes in secondary structure with a strong increase in antiparallel β sheet...

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Autori principali: Zeitler, Marcel (Autore) , Steringer, Julia P. (Autore) , Müller, Hans-Michael (Autore) , Mayer, Matthias P. (Autore) , Nickel, Walter (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: July 16, 2015
In: The journal of biological chemistry
Year: 2015, Volume: 290, Fascicolo: 36, Pages: 21976-21984
ISSN:1083-351X
DOI:10.1074/jbc.M115.667097
Accesso online:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M115.667097
Verlag, lizenzpflichtig, Volltext: http://www.jbc.org/content/290/36/21976
Testo
Note sull'autore:Marcel Zeitler, Julia P. Steringer, Hans-Michael Müller, Matthias P. Mayer, and Walter Nickel
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Riassunto:HIV-Tat has been demonstrated to be secreted from cells in a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-dependent manner. Here we show that HIV-Tat forms membrane-inserted oligomers, a process that is accompanied by changes in secondary structure with a strong increase in antiparallel β sheet content. Intriguingly, oligomerization of HIV-Tat on membrane surfaces leads to the formation of membrane pores, as demonstrated by physical membrane passage of small fluorescent tracer molecules. Although membrane binding of HIV-Tat did not strictly depend on PI(4,5)P2 but, rather, was mediated by a range of acidic membrane lipids, a functional interaction between PI(4,5)P2 and HIV-Tat was critically required for efficient membrane pore formation by HIV-Tat oligomers. These properties are strikingly similar to what has been reported previously for fibroblast growth factor 2 (FGF2), providing strong evidence of a common core mechanism of unconventional secretion shared by HIV-Tat and fibroblast growth factor 2.
Descrizione del documento:Gesehen am 21.07.2020
Descrizione fisica:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M115.667097