7MRL

Structure of HIV-1 matrix domain bound to human tRNALys3

Summary for 7MRL

• Entry DOI: 10.2210/pdb7mrl/pdb
• Descriptor: HIV-1 matrix domain, tRNA Lys3, MAGNESIUM ION (3 entities in total)
• Functional Keywords: hiv-1, gag, matrix domain, rna-protein interaction, trna, transfer rna, ribonucleoprotein complex, viral protein-rna complex, viral protein/rna
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 3
• Total formula weight: 48816.67

Authors

Bou-Nader, C.,Zhang, J. (deposition date: 2021-05-07, release date: 2021-08-11, Last modification date: 2023-10-25)

Primary citation

Bou-Nader, C.,Muecksch, F.,Brown, J.B.,Gordon, J.M.,York, A.,Peng, C.,Ghirlando, R.,Summers, M.F.,Bieniasz, P.D.,Zhang, J.
HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization.
Cell Host Microbe, 29:1421-, 2021

PubMed 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-tRNA 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.

PubMed: 34384537
DOI: 10.1016/j.chom.2021.07.006

Experimental method

X-RAY DIFFRACTION (3.15 Å)