Nature Structural & Molecular Biology
12, 671 - 677 (2005)
Published online: 24 July 2005; | doi:10.1038/nsmb964
A peptide inhibitor of HIV-1 assembly in vitroJana Sticht1, Michael Humbert2, Stuart Findlow3, Jochen Bodem1, Barbara Müller1, Ursula Dietrich2, Jörn Werner3
& Hans-Georg Kräusslich11
Department of Virology, Universitätsklinikum Heidelberg, 69120
Heidelberg, Germany. 2
Institute for Biomedical Research, Georg-Speyer-Haus, 60596
Frankfurt/Main, Germany. 3
School of Biological Sciences, University of Southampton, Southampton
SO16 7PX, UK.
Correspondence should be addressed to Hans-Georg Kräusslich hans-georg.kraeusslich@med.uni-heidelberg.de 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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