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Glycoproteins gp120 and gp41 are part of the AIDS HIV virus envelope. These proteins are involved in both, virus / host cell membrane fusion, a step essential for viral infection, and in the immune response to the virus. The knowledge of the structure of these proteins is crucial to understand these mechanisms at molecular level.
Scientists from the NMR group at the Institute of Physical-Chemistry ‘Rocasolano’ (CSIC), in collaboration with Dr. J. L. Nieva (University of the Basque Country) and Dr. J.M.M. Caaveiro (University of Tokyo) have determined the structure of several peptides reproducing sequences of the MPER (membrane-proximal external region) and TM (trans-membrane) sub-domains of the HIV gp41 protein. This work shows that the structure of the trans-membrane region, which has not been solved previously, presents two helices connected by a flexible segment. In addition, it has been found that the final MPER region and the initial TM region form a unique uninterrupted helix, in contrast to bioinformatics prediction. A model for the mechanism of virus / host cell membrane fusion has been proposed on the basis of these structural data. More interestingly, these data also explain the observed differences in antibody affinity, as well as the immune response of MPER-derived peptides. Accordingly, this information would be of great interest for a rational design of novel vaccines and inhibitors, useful as alternative therapies against AIDS.
The work has been selected as “Paper of the Week” by the editors of J. Biol. Chem.
Virion and envelope glycoprotein contour images were kindly provided by Dr. S. Subramaniam.
B. Apellaniz, E. Rojas, S. Serrano, K. Morante, K. Tsumoto, J.M.M. Caaveiro, M.A. Jiménez, & J.L. Nieva. “The atomic structure of the HIV-1 gp41 MPER-TMD region reveals a continuously helical inter-domain connection flanked by two metastable hinge segments. Implications for MPER immunogenicity”. J. Biol. Chem. (2015). doi:10.1074/jbc.M115.644351.
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