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The postfusion structure of baculovirus gp64 supports a unified view of viral fusion machines

Abstract

Viral fusion proteins mediate the merger of host and viral membranes during cell entry for all enveloped viruses. Baculovirus glycoprotein gp64 (gp64) is unusual in promoting entry into both insect and mammalian cells and is distinct from established class I and class II fusion proteins. We report the crystal structure of its postfusion form, which explains a number of gp64′s biological properties including its cellular promiscuity, identifies the fusion peptides and shows it to be the third representative of a new class (III) of fusion proteins with unexpected structural homology with vesicular stomatitis virus G and herpes simplex virus type 1 gB proteins. We show that domains of class III proteins have counterparts in both class I and II proteins, suggesting that all these viral fusion machines are structurally more related than previously thought.

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Figure 1: Overall structure of gp64.
Figure 2: pH-sensitive interfaces of gp64.
Figure 3: gp64 fusion loops.
Figure 4: Structural similarities among the class I, II and III fusion proteins domains.

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Acknowledgements

The work was supported by grants from the UK Medical Research Council to D.I.S. and I.M.J. J.K. was supported by a long term fellowship from the European Molecular Biology Organisation (EMBO). We thank M. Walsh for assistance during the data collection at the UK MAD beamline BM14 at the European Synchrotron Radiation Facility and R. Aricescu for help with syncytium-formation assays. We also thank L. Volkman (University of California) for the gift of the B12D5 monoclonal antibody and K. Harlos for the help with heavy-atom derivatives.

Author information

Authors and Affiliations

Authors

Contributions

S.L. and I.M.J. expressed and purified the protein; J.K. and N.G.A.A. obtained crystals, and solved and refined the structure; J.K. and S.L. performed syncytium-formation assays; J.K., D.I.S. and I.M.J. analyzed the structure and wrote the manuscript.

Corresponding author

Correspondence to David I Stuart.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 (PDF 4395 kb)

Supplementary Video 1

Transition of dengue virus E domain III to HSV-1 gB domain IV, first superposed with program SHP. Structurally equivalent residues are shown in red, while areas where major changes occur are in green. Domain boundaries and orientation correspond to the ones in Figure 4. (MOV 1461 kb)

Supplementary Video 2

Transition of paramyxovirus F domain I to gp64 domain Ib, first superposed with program SHP. Structurally equivalent residues are shown in red, while areas where major changes occur are in green. Domain boundaries and orientation correspond to the ones in Figure 4. (MOV 807 kb)

Supplementary Video 3

Transition of dengue virus E domain IIa to VSV G domain Ib, first superposed with program SHP. Structurally equivalent residues are shown in red, while areas where major changes occur are in green. Domain boundaries and orientation correspond to the ones in Figure 4. (MOV 940 kb)

Supplementary Video 4

Transition of paramyxovirus F domain III to dengue virus E domain IIa, first superposed with program SHP. For clarity, the helical insertion of paramyxovirus F protein (56-239) is not shown, and residues 55 and 240 are connected. Structurally equivalent residues are shown in red, while areas where major changes occur are in green. Domain boundaries and orientation correspond to the ones in Figure 4. (MOV 1011 kb)

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Kadlec, J., Loureiro, S., Abrescia, N. et al. The postfusion structure of baculovirus gp64 supports a unified view of viral fusion machines. Nat Struct Mol Biol 15, 1024–1030 (2008). https://doi.org/10.1038/nsmb.1484

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