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  • The EMBO Journal (1999) 18, 1124 - 1136
  • doi:10.1093/emboj/18.5.1124

Head-to-tail dimers and interdomain flexibility revealed by the crystal structure of HIV-1 capsid protein (p24) complexed with a monoclonal antibody Fab

Carmen Berthet-Colominas1,4, Stéphanie Monaco1,4, Armelle Novelli2, Geneviève Sibaï3, François Mallet2 and Stephen Cusack1

  1. European Molecular Laboratory Biology, Grenoble Outstation, B.P.156X, F-38042 Grenoble Cedex 9, France
  2. Unité Mixte 103 CNRS-bioMérieux, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cédex 07, France
  3. bioMérieux, Chemin de l'Orme, 69820 Marcy l'Etoile, France
  4. C.Berthet-Colominas and S.Monaco contributed equally to this work

Correspondence to:

Stephen Cusack, E-mail: cusack@embl-grenoble.fr

Received 8 September 1998; Accepted 7 January 1999; Revised 30 December 1998

The crystal structure of an intact molecule of HIV-1 capsid protein (p24) in complex with a monoclonal antibody fragment recognizing an epitope on the C-terminal domain has been determined at 3 Å resolution. The helical N- and C-terminal domains of p24 are linked by an extended peptide forming a flexibly linked dumb-bell-shaped molecule 75 Å in overall length. The p24 construct used is a variant with an N-terminal extension that mimics to some extent the Gag context of p24. We observed a novel head-to-tail dimer of p24 molecules which occurs through the formation of a substantial intermolecular interface between the N- and C-terminal domains. Comparison with previously observed p24 dimers shows that the same residues and secondary structural elements can partake in different interfaces revealing a remarkable stickiness and plasticity of the p24 molecule, properties which, combined with the inter-domain flexibility, are presumably important in the assembly and maturation of viral particles. Previous mutagenesis studies designed to test specific N–N and C–C homodimer interfaces do not discriminate fully against the possibility of the observed N–C interface.

  • Keywords:

    • Fab,
    • HIV-1,
    • p24,
    • virus assembly,
    • X-ray crystallography