A peptide inhibitor of HIV-1 assembly in vitro


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).

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Original Publication URL: http://dx.doi.org/10.1038/nsmb964

Description/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.

Item Type: Article
ISSNs: 1545-9993 (print)
Related URLs:
Keywords: human-immunodeficiency-virus, type-1 particle formation, c-terminal domain, capsid protein, dimerization domain, gag protein, core, saturation, resolution, morphogenesis
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 24036
Date Deposited: 17 Mar 2006
Last Modified: 14 Apr 2014 09:18
Projects:
Structure and mechanism of a novel HIV assembly inhibitor
Funded by: BBSRC (BB/D005000/1)
Led by: Joern Martin Werner
1 August 2006 to 31 January 2010
URI: http://eprints.soton.ac.uk/id/eprint/24036

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