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PDBsum entry 1qr9
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Viral protein
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PDB id
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1qr9
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Inhibition of human immunodeficiency virus type 1 infectivity by the gp41 core: role of a conserved hydrophobic cavity in membrane fusion.
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Authors
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H.Ji,
W.Shu,
F.T.Burling,
S.Jiang,
M.Lu.
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Ref.
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J Virol, 1999,
73,
8578-8586.
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PubMed id
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Abstract
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The gp41 envelope protein of human immunodeficiency virus type 1 (HIV-1)
contains an alpha-helical core structure responsible for mediating membrane
fusion during viral entry. Recent studies suggest that a conserved hydrophobic
cavity in the coiled coil of this core plays a distinctive structural role in
maintaining the fusogenic conformation of the gp41 molecule. Here we
investigated the importance of this cavity in determining the structure and
biological activity of the gp41 core by using the N34(L6)C28 model. The
high-resolution crystal structures of N34(L6)C28 of two HIV-1 gp41
fusion-defective mutants reveal that each mutant sequence is accommodated in the
six-helix bundle structure by forming the cavity with different sets of atoms.
Remarkably, the mutant N34(L6)C28 cores are highly effective inhibitors of HIV-1
infection, with 5- to 16-fold greater activity than the wild-type molecule. The
enhanced inhibitory activity by fusion-defective mutations correlates with local
structural perturbations close to the cavity that destabilize the six-helix
bundle. Taken together, these results indicate that the conserved hydrophobic
coiled-coil cavity in the gp41 core is critical for HIV-1 entry and its
inhibition and provides a potential antiviral drug target.
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