Structural insight into HIV-1 capsid recognition by rhesus TRIM5α.

Yang H, Ji X, Zhao G, Ning J, Zhao Q, Aiken C, Gronenborn AM, Zhang P, Xiong Y
Proc Natl Acad Sci U S A. 2012 109 (45): 18372-7

PMID: 23091002 · PMCID: PMC3494900 · DOI:10.1073/pnas.1210903109

Tripartite motif protein isoform 5 alpha (TRIM5α) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5α recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner. Upon binding, TRIM5α induces premature disassembly of the viral capsid and activates the downstream innate immune response. We have determined the crystal structure of the rhesus TRIM5α PRY/SPRY domain that reveals essential features for capsid binding. Combined cryo-electron microscopy and biochemical data show that the monomeric rhesus TRIM5α PRY/SPRY, but not the human TRIM5α PRY/SPRY, can bind to HIV-1 capsid protein assemblies without causing disruption of the capsid. This suggests that the PRY/SPRY domain alone constitutes an important pattern-sensing component of TRIM5α that is capable of interacting with viral capsids of different curvatures. Our results provide molecular insights into the mechanisms of TRIM5α-mediated retroviral restriction.

MeSH Terms (16)

Amino Acid Sequence Animals Capsid Carrier Proteins Conserved Sequence Crystallography, X-Ray Evolution, Molecular HIV-1 Humans Macaca mulatta Models, Molecular Molecular Sequence Data Protein Binding Protein Multimerization Protein Structure, Tertiary Solutions

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