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Internal Dynamics of the Homotrimeric HIV-1 Viral Coat Protein gp41 on Multiple Time Scales

Authors

  • Dr. Nils-Alexander Lakomek,

    1. Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Building 5, Room 126, 9000 Rockville Pike, Bethesda, MD 20892-0520 (USA)
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  • Joshua D. Kaufman,

    1. Protein Expression Laboratory, NIAMS, National Institutes of Health, Building 6B, Room 1B130 (USA)
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  • Dr. Stephen J. Stahl,

    1. Protein Expression Laboratory, NIAMS, National Institutes of Health, Building 6B, Room 1B130 (USA)
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  • Dr. John M. Louis,

    1. Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Building 5, Room 126, 9000 Rockville Pike, Bethesda, MD 20892-0520 (USA)
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  • Dr. Alexander Grishaev,

    1. Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Building 5, Room 126, 9000 Rockville Pike, Bethesda, MD 20892-0520 (USA)
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  • Dr. Paul T. Wingfield,

    1. Protein Expression Laboratory, NIAMS, National Institutes of Health, Building 6B, Room 1B130 (USA)
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  • Dr. Ad Bax

    Corresponding author
    1. Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Building 5, Room 126, 9000 Rockville Pike, Bethesda, MD 20892-0520 (USA)
    • Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Building 5, Room 126, 9000 Rockville Pike, Bethesda, MD 20892-0520 (USA)
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  • We thank Yang Shen for expert advice and Jinfa Ying and James Baber for experimental assistance. This research was funded by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) and the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. We acknowledge use of the shared scattering beamline resource allocated under the PUP-77 agreement between the National Cancer Institute and the Argonne National Laboratory and thank Dr. Soenke Seifert (Argonne National Laboratory) for his support of the SAXS experiments. Use of the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under Contract W-31-109-ENG-38. HIV=human immunodeficiency virus.

Abstract

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Always on the move: Solution NMR spectroscopy revealed a high degree of intrinsic mobility for the homotrimeric viral coat protein gp41: a prehairpin intermediate (left) may sample a range of relative orientations of the C-terminal and N-terminal heptad repeats, possibly in exchange with a low population of the late-fusion six-helical bundle (right; FP: fusion peptide, TM: transmembrane helix).

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