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A peptide inhibitor of HIV-1 assembly in vitro

Record type: Article

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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Citation

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

More information

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
ORCID for Jörn Werner: ORCID iD orcid.org/0000-0002-4712-1833

Catalogue record

Date deposited: 17 Mar 2006
Last modified: 17 Jul 2017 16:15

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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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