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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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Bibliographic Details
Main Authors: Zeitler, Marcel (Author) , Steringer, Julia P. (Author) , Müller, Hans-Michael (Author) , Mayer, Matthias P. (Author) , Nickel, Walter (Author)
Format: Article (Journal)
Language:English
Published: July 16, 2015
In: The journal of biological chemistry
Year: 2015, Volume: 290, Issue: 36, Pages: 21976-21984
ISSN:1083-351X
DOI:10.1074/jbc.M115.667097
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M115.667097
Verlag, lizenzpflichtig, Volltext: http://www.jbc.org/content/290/36/21976
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Author Notes:Marcel Zeitler, Julia P. Steringer, Hans-Michael Müller, Matthias P. Mayer, and Walter Nickel
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Summary: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.
Item Description:Gesehen am 21.07.2020
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M115.667097

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