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.