A peptide inhibitor of HIV-1 assembly in vitro
A peptide inhibitor of HIV-1 assembly in vitro
Formation of infectious HIV-1 involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids after proteolytic disassembly of the Gag shell. We report a 12-mer peptide, capsid assembly inhibitor (CAI), that binds the capsid (CA) domain of Gag and inhibits assembly of immature- and mature-like capsid particles in vitro. CAI was identified by phage display screening among a group of peptides with similar sequences that bind to a single reactive site in CA. Its binding site was mapped to CA residues 169-191, with an additional contribution from the last helix of CA. This result was confirmed by a separate X-ray structure analysis showing that CAI inserts into a conserved hydrophobic groove and alters the CA dimer interface. The CAI binding site is a new target for antiviral development, and CAI is the first known inhibitor directed against assembly of immature HIV-1.
human-immunodeficiency-virus, type-1 particle formation, c-terminal domain, capsid protein, dimerization domain, gag protein, core, saturation, resolution, morphogenesis
671-677
Sticht, Jana
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Humbert, Michael
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Findlow, Stuart C.
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Bodem, Jochen
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Müller, Barbara
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Dietrich, Ursula
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Werner, Jörn
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Kräusslich, Hans-Georg
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24 July 2005
Sticht, Jana
ab6370c9-0538-4fca-9340-cf02f0b64a74
Humbert, Michael
c74c1327-26d0-4354-8e74-483248bd6b8b
Findlow, Stuart C.
0a7193ad-45cf-4613-a35e-3fd019a92ebe
Bodem, Jochen
2f6465f4-d646-4100-b521-bd83858c19d7
Müller, Barbara
3e312bbe-1e4e-4145-8a7a-4240adf15b41
Dietrich, Ursula
ae2a30aa-3fd0-445b-ba19-83541e3e3eb6
Werner, Jörn
1b02513a-8310-4f4f-adac-dc2a466bd115
Kräusslich, Hans-Georg
3bcb0af4-b2ce-442c-8cec-b2e73732549c
Sticht, Jana, Humbert, Michael, Findlow, Stuart C., Bodem, Jochen, Müller, Barbara, Dietrich, Ursula, Werner, Jörn and Kräusslich, Hans-Georg
(2005)
A peptide inhibitor of HIV-1 assembly in vitro.
Nature Structural & Molecular Biology, 12 (8), .
(doi:10.1038/nsmb964).
Abstract
Formation of infectious HIV-1 involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids after proteolytic disassembly of the Gag shell. We report a 12-mer peptide, capsid assembly inhibitor (CAI), that binds the capsid (CA) domain of Gag and inhibits assembly of immature- and mature-like capsid particles in vitro. CAI was identified by phage display screening among a group of peptides with similar sequences that bind to a single reactive site in CA. Its binding site was mapped to CA residues 169-191, with an additional contribution from the last helix of CA. This result was confirmed by a separate X-ray structure analysis showing that CAI inserts into a conserved hydrophobic groove and alters the CA dimer interface. The CAI binding site is a new target for antiviral development, and CAI is the first known inhibitor directed against assembly of immature HIV-1.
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Published date: 24 July 2005
Keywords:
human-immunodeficiency-virus, type-1 particle formation, c-terminal domain, capsid protein, dimerization domain, gag protein, core, saturation, resolution, morphogenesis
Identifiers
Local EPrints ID: 24036
URI: http://eprints.soton.ac.uk/id/eprint/24036
ISSN: 1545-9993
PURE UUID: d0ee776a-34a7-4ace-bca6-8335e64d53c1
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Date deposited: 17 Mar 2006
Last modified: 16 Mar 2024 03:36
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Contributors
Author:
Jana Sticht
Author:
Michael Humbert
Author:
Stuart C. Findlow
Author:
Jochen Bodem
Author:
Barbara Müller
Author:
Ursula Dietrich
Author:
Hans-Georg Kräusslich
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