Characterization of the Interaction of Two Peptides from the N Terminus of the NHR Domain of HIV-1 gp41 with Phospholipid Membranes

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• 作者：Miguel R. Moreno ; Jaime Guillé ; n ; Ana J. Pé ; rez-Bern&aacute ; Diego Amoró ; s ; Ana I. Gó ; mez ; &Aacute ; ngela Bernabeu ; José ; Villalaí ; n
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：September 18, 2007
• 年：2007
• 卷：46
• 期：37
• 页码：10572 - 10584
• 全文大小：522K
• 年卷期：v.46,no.37(September 18, 2007)
• ISSN：1520-4995

文摘

The HIV-1 gp41 envelope glycoprotein is responsible for the membrane fusion between thevirus and the target cell. According to recent models, the N-terminal coiled-coil (NHR) region of gp41 isinvolved in forming the interfaces between neighboring helices in the six-helix bundle, as well as inmembrane binding and perturbation. In order to get new insights into the viral membrane fusion mechanism,two peptides, pFP₁₅ and pFP₂₃, pertaining to the first part of the gp41 NHR domain were studied regardingtheir structure and their ability to induce membrane leakage, aggregation, and fusion, as well as theiraffinity toward specific phospholipids by a variety of spectroscopic methods. Our results demonstratethat the first part of the NHR domain interacts with negatively charged phospholipid-containing modelmembranes, modifies the phase behavior of membrane phospholipids, and induces leakage and aggregationof liposomes, suggesting that it could be involved directly in the merging of the viral and target cellmembranes working synergistically with other membrane-active regions of the gp41 glycoprotein to boostthe fusion process. On the other hand, we suggest that this region of the NHR domain could be involvedin the first steps of the destabilization of the HIV-1 gp41 six-helix bundle after its interaction with negativelycharged phospholipid headgroups.