Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.
Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.
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DOI：
10.1042/bj20140189
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发表时间：
2014-07-15
期刊：
影响因子：
--
通讯作者：
Shai Y
中科院分区：
文献类型：
--
作者：
Klug YA;Ashkenazi A;Viard M;Porat Z;Blumenthal R;Shai Y
Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus–cell and cell–cell contact sites. Overall, the findings of the present study may suggest lipid–protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes. We show that sphinganine lipidated peptides affect membrane fusion, modulate the membrane and disrupt protein assembly. In addition the findings may aid in deciphering the function of DHSM in biological membranes.
