HIV-1 Matrix Protein Interactions with tRNA: Implications for Membrane Targeting

Journal of Molecular Biology
Christy R GainesMichael F Summers

Abstract

The N-terminally myristoylated matrix (MA) domain of the HIV-1 Gag polyprotein promotes virus assembly by targeting Gag to the inner leaflet of the plasma membrane. Recent studies indicate that, prior to membrane binding, MA associates with cytoplasmic tRNAs (including tRNALys3), and in vitro studies of tRNA-dependent MA interactions with model membranes have led to proposals that competitive tRNA interactions contribute to membrane discrimination. We have characterized interactions between native, mutant, and unmyristylated (myr-) MA proteins and recombinant tRNALys3 by NMR spectroscopy and isothermal titration calorimetry. NMR experiments confirm that tRNALys3 interacts with a patch of basic residues that are also important for binding to the plasma membrane marker, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Unexpectedly, the affinity of MA for tRNALys3 (Kd = 0.63 ± 0.03 μM) is approximately 1 order of magnitude greater than its affinity for PI(4,5)P2-enriched liposomes (Kd(apparent) = 10.2 ± 2.1 μM), and NMR studies indicate that tRNALys3 binding blocks MA association with liposomes, including those enriched with PI(4,5)P2, phosphatidylserine, and cholesterol. However, the affinity of MA for tRNALys3 is diminished by...Continue Reading

Citations

Aug 4, 2019·Journal of Virology·Ayna AlfadhliEric Barklis
Oct 2, 2019·The Journal of Biological Chemistry·Huaying ZhaoPeter Schuck
Oct 4, 2020·Viruses·Patricia S BoydSaif Yasin
Apr 4, 2021·International Journal of Molecular Sciences·Charlotte BussienneSerena Bernacchi
Aug 6, 2021·Scientific Reports·Halilibrahim CiftciHasan DeMirci
Aug 7, 2021·Science·Kun QuJohn A G Briggs
Aug 14, 2021·Cell Host & Microbe·Charles Bou-NaderJinwei Zhang
May 16, 2019·The Journal of Physical Chemistry. B·Renee J TranJohn C Conboy

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