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A peptide inhibitor of HIV-1 assembly in vitro

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
1545-9993
671-677
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
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), 671-677. (doi:10.1038/nsmb964).

Record type: Article

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: https://eprints.soton.ac.uk/id/eprint/24036
ISSN: 1545-9993
PURE UUID: d0ee776a-34a7-4ace-bca6-8335e64d53c1
ORCID for Jörn Werner: ORCID iD orcid.org/0000-0002-4712-1833

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Date deposited: 17 Mar 2006
Last modified: 06 Jun 2018 12:45

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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: Jörn Werner ORCID iD
Author: Hans-Georg Kräusslich

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