Conformational study of fragments of envelope proteins (gp120: 254–274 and gp41: 519–541) of HIV-1 by NMR and MD simulations
✍ Scribed by Meena Kanyalkar; Sudha Srivastava; Anil Saran; Evans Coutinho
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 357 KB
- Volume
- 10
- Category
- Article
- ISSN
- 1075-2617
- DOI
- 10.1002/psc.530
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✦ Synopsis
Abstract
The envelope proteins, gp120 and gp41 of HIV‐1, play a crucial role in receptor (CD4^+^ lymphocytes) binding and membrane fusion. The fragment 254–274 of gp120 is conserved in all strains of HIV and, as a part of the full gp120 protein, behaves as ‘immunosilent’, but as an individual fragment it is ‘immunoreactive’. When this fragment binds to its receptor, it activates the fusion domain of gp41 allowing viral entry into the host CD4^+^ cells. The conformation of fragment 254–274 of the gp120 domain and fragment 519–541 of the gp41 domain was studied by NMR and MD simulations. The studies were carried out in three varied media—water, DMSO‐d~6~ and hexafluoroacetone (HFA). The fusogenic nature of the gp41 domain peptide was investigated by ^31^P NMR experiments with model bilayers prepared from dimyristoyl‐L‐α‐phosphatidylcholine (DMPC). The solvent was seen to exert a major effect on the structure of the two peptides. Fragment (254–274) of gp120 in DMSO‐d~6~ had a type I β‐turn around the tetrad Val^9^‐Ser^10^‐Thr^11^‐Gln^12^ while in HFA a helical structure spanning the region Ile^5^ to Gln^12^ was seen with the remaining part of the peptide in a random coil structure. It is possible that the β‐turn may constitute an initiation site for the formation of the helix. In water at pH 4.5, the peptide adopted a β‐sheet. The NMR results for fragment 519–541 of gp41 are conclusive of a β‐sheet structure in DMSO‐d~6~, a conformation which may help in insertion into the membrane, a notion also put forward by others. The ^31^P NMR studies of DMPC vesicles with this fragment show its fusogenic nature, promoting fusion of unilamellar vesicles to larger agglomerates like multilamellar ones. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.