title: Structural insight into HIV-1 capsid recognition by rhesus TRIM5α.
abstract: 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ji
authors.forename: Gongpu
authors.initials: G
authors.lastname: Zhao
authors.forename: Jiying
authors.initials: J
authors.lastname: Ning
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
authors.forename: Peijun
authors.initials: P
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008253:Macaca mulatta / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D002352:Carrier Proteins; D012996:Solutions