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Publication Abstract from PubMed

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-tRNA(Lys3) 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.

HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization.,Bou-Nader C, Muecksch F, Brown JB, Gordon JM, York A, Peng C, Ghirlando R, Summers MF, Bieniasz PD, Zhang J Cell Host Microbe. 2021 Sep 8;29(9):1421-1436.e7. doi: , 10.1016/j.chom.2021.07.006. Epub 2021 Aug 11. PMID:34384537^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.