HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization

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https://www.sciencedirect.com/science/article/pii/S1931312821003395?via%3Dihub#!

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https://doi.org/10.1016/j.chom.2021.07.006
 http://hdl.handle.net/11603/22673

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UMBC Chemistry & Biochemistry Department
UMBC Faculty Collection

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Author/Creator ORCID

https://orcid.org/0000-0001-5986-8902

Date

2021-08-11

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journal articles
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Citation of Original Publication

Bou-Nader, Charles et al.; HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization; Cell Host & Microbe, 11 August, 2021; https://doi.org/10.1016/j.chom.2021.07.006

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Abstract

The HIV-1 virion structural polyprotein, Gag, is directed to particle assembly sites at the plasma membrane by its N-terminal matrix (MA) domain. MA also binds to host tRNAs. To understand the molecular basis of MA-tRNA interaction and its potential function, we present a co-crystal structure of HIV-1 MA-tRNALys3 complex. The structure reveals a specialized group of MA basic and aromatic residues preconfigured to recognize the distinctive structure of the tRNA elbow. Mutational, cross-linking, fluorescence, and NMR analyses show that the crystallographically defined interface drives MA-tRNA binding in solution and living cells. The structure indicates that MA is unlikely to bind tRNA and membrane simultaneously. Accordingly, single-amino-acid substitutions that abolish MA-tRNA binding caused striking redistribution of Gag to the plasma membrane and reduced HIV-1 replication. Thus, HIV-1 exploits host tRNAs to occlude a membrane localization signal and control the subcellular distribution of its major structural protein.