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

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Abstract
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.