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

Publication Type:

Journal Article

Authors:

Yang, Haitao; Ji, Xiaoyun; Zhao, Gongpu; Ning, Jiying; Zhao, Qi; Aiken, Christopher; Gronenborn, Angela M; Zhang, Peijun; Xiong, Yong

Source:

Proc Natl Acad Sci U S A, Volume 109, Issue 45, p.18372-7 (2012)

Keywords:

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

Abstract:

<p>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.</p>