General model for retroviral capsid pattern recognition by TRIM5 proteins
Wagner, Jonathan M.
Christensen, Devin E.
Dawidziak, Daria M.
Roganowicz, Marcin D.
Pumroy, Ruth A.
Ivanov, Dmitri N.
Ganser-Pornillos, Barbie K.
American Society for Microbiology
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
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Pattern recognition , Restriction factor , Retrovirus , TRIM5 proteins
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