Rhesus TRIM5α Disrupts the HIV-1 Capsid at the Inter­Hexamer Interfaces

• DOI: 10.1371/journal.ppat.1002009
• Publication Date: 2011-03-24T20:55:40Z
• Authors: Gongpu Zhao; Danxia Ke; Thomas Vu; Jinwoo Ahn; Vaibhav B. Shah; Ruifeng Yang; Christopher Aiken; Lisa M. Charlton; Angela M. Gronenborn; Peijun Zhang
• Keywords: Random hexamer; Trimer

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of assembled is essential for restriction requires coiled-coil B30.2/SPRY domains, but molecular mechanism not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis chemical cross-linking, direct interactions between protein (CA) assemblies purified TRIM5αrh containing SPRY domains (CC-SPRYrh). Concentration-dependent CC-SPRYrh CA was observed, while under equivalent conditions did bind. Importantly, CC-SPRYrh, its counterpart, disrupted tubes a non-random fashion, releasing fragments protofilaments consisting hexamers without dissociation into monomers. Furthermore, such structural destruction prevented inter-hexamer crosslinking using P207C/T216C mutant disulfide bonds CTD-CTD trimer interface assemblies, intra-hexamer via A14C/E45C NTD-NTD interface. The same disruption effect on interfaces also occurred intact cores. These results provide insights concerning how disrupts virion core demonstrate damage viral likely one components TRIM5α-mediated restriction.