General model for retroviral capsid pattern recognition by TRIM5 proteins
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Date
2018
Authors
Wagner, Jonathan M.
Christensen, Devin E.
Bhattacharya, Akash
Dawidziak, Daria M.
Roganowicz, Marcin D.
Wan, Yueping
Pumroy, Ruth A.
Demeler, Borries
Ivanov, Dmitri N.
Ganser-Pornillos, Barbie K.
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract
Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity (KD of >1 mM) and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher affinity (KD of ∼10 μM) for isolated capsid subunits. Therefore, it has been argued that TRIMCyp proteins have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5α, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition
Description
Permission to archive final published version
Keywords
Pattern recognition , Restriction factor , Retrovirus , TRIM5 proteins
Citation
Wagner, J. M., Christensen, D. E., Bhattacharya, A., Dawidziak, D. M., Roganowicz, M. D., Wan, Y., Pumroy, R. A., Demeler, B., Ivanov, D. N., Ganser-Pornillos, B. K., Sundquist, W. I., & Pornillow, O. (2018). General model for retroviral capsid pattern recognition by TRIM5 proteins. Journal of Virology, 92(4), Article e01563-17. https://doi.org/10.1128/JVI.01563-17