Characterization of the interaction of two peptides from the N terminus of the NHR domain of HIV-1 gp41 with phospholipid membranes.
The HIV-1 gp41 envelope glycoprotein is responsible for the membrane fusion between the virus and the target cell. According to recent models, the N-terminal coiled-coil (NHR) region of gp41 is involved in forming the interfaces between neighboring helices in the six-helix bundle, as well as in membrane 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 regarding their structure and their ability to induce membrane leakage, aggregation, and fusion, as well as their affinity toward specific phospholipids by a variety of spectroscopic methods. Our results demonstrate that the first part of the NHR domain interacts with negatively charged phospholipid-containing model membranes, modifies the phase behavior of membrane phospholipids, and induces leakage and aggregation of liposomes, suggesting that it could be involved directly in the merging of the viral and target cell membranes working synergistically with other membrane-active regions of the gp41 glycoprotein to boost the fusion process. On the other hand, we suggest that this region of the NHR domain could be involved in the first steps of the destabilization of the HIV-1 gp41 six-helix bundle after its interaction with negatively charged phospholipid headgroups.
Moreno
Miguel R
MR
Instituto de Biología Molecular y Celular, Campus de Elche, Universidad Miguel HernAndez, E-03202 Elche-Alicante, Spain.
Guillén
Jaime
J
Pérez-Berna
Ana J
AJ
Amorós
Diego
D
Gómez
Ana I
AI
Bernabeu
Angela
A
Villalaín
José
J
D000595:Amino Acid Sequence; D016880:Anisotropy; D002942:Circular Dichroism; D005453:Fluorescence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053835:Unilamellar Liposomes / Q000378:metabolism*
D015700:HIV Envelope Protein gp41; D010455:Peptides; D010743:Phospholipids; D053835:Unilamellar Liposomes