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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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.
|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
|Date Deposited:||17 Mar 2006|
|Last Modified:||28 Jun 2012 10:02|
|Contact Email Address:||firstname.lastname@example.org|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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