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Atomic structure of the ectodomain from HIV-1 gp41

Nature volume 387, pages 426–430 (1997)Cite this article

Abstract

Fusion of viral and cellular membranes by the envelope glyco-protein gp120/gp41 effects entry of HIV-1 into the cell. The precursor, gp160, is cleaved post-translationally into gp120 and gp41 (refs 1,2), which remain non-covalently associated. Binding to both CD4 and a co-receptor leads to the conformational changes in gp120/gp41 needed for membrane fusion3. We used X-ray crystallography to determine the structure of the protease-resistant part4,5 of a gp41 ectodomain solubilized with a trimeric GCN4 coiled coil in place of the amino-terminal fusion peptide6. The core of the molecule is found to be an extended, triple-stranded a-helical coiled coil with the amino terminus at its tip. A carboxy-terminal α-helix packs in the reverse direction against the outside of the coiled coil, placing the amino and carboxy termini near each other at one end of the long rod. These features, and the existence of a similar reversal of chain direction in the fusion pH-induced conformation of influenza virus HA2 (ref. 7) and in the transmembrane subunit of Moloney murine leukaemia virus8 (Fig. la–d), suggest a common mechanism for initiating fusion.

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Author notes

  1. W. Weissenhorn and A. Dessen: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Molecular Medicine, The Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts, 02215, USA

    W. Weissenhorn, A. Dessen, S. C. Harrison & D. C. Wiley

  2. Howard Hughes Medical Institute, The Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts, 02215, USA

    W. Weissenhorn, S. C. Harrison & D. C. Wiley

  3. Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    S. C. Harrison & D. C. Wiley

  4. National Institute of Medical Research, Mill Hill, The Ridgeway, London, NW7 1AA, UK

    J. J. Skehel

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  4. J. J. Skehel
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Weissenhorn, W., Dessen, A., Harrison, S. et al. Atomic structure of the ectodomain from HIV-1 gp41. Nature 387, 426–430 (1997). https://doi.org/10.1038/387426a0

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