期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：45
页码：18372-18377
DOI：10.1073/pnas.1210903109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Tripartite motif protein isoform 5 alpha (TRIM5) is a potent antiviral protein that restricts infection by HIV-1 and other retroviruses. TRIM5 recognizes the lattice of the retrovirus capsid through its B30.2 (PRY/SPRY) domain in a species-specific manner. Upon binding, TRIM5 induces premature disassembly of the viral capsid and activates the downstream innate immune response. We have determined the crystal structure of the rhesus TRIM5 PRY/SPRY domain that reveals essential features for capsid binding. Combined cryo-electron microscopy and biochemical data show that the monomeric rhesus TRIM5 PRY/SPRY, but not the human TRIM5 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 TRIM5 that is capable of interacting with viral capsids of different curvatures. Our results provide molecular insights into the mechanisms of TRIM5-mediated retroviral restriction.
