Beschreibung:
<jats:sec><jats:label /><jats:p>The human immunodeficiency virus (HIV) is a retrovirus that infects roughly 40 million people globally that attacks CD4<jats:sup>+</jats:sup> T‐cells, thus impairing the immune system. Highly active antiretroviral treatment against the virus is available; however, the viral genome frequently mutates, which gives rise to evasion of current therapies and highlights the need for new drugs. Better understanding molecular mechanisms of viral replication may lend to this effort. One process necessary for HIV replication is membrane trafficking of the Gag polyprotein (Gag) to the plasma membrane via Gag’s N‐terminal matrix domain (MA). MA mediates membrane targeting by means of electrostatic interaction and anchoring to the plasma membrane using a covalently linked myristoyl moiety. Recent virology studies demonstrated that MA interacts with cellular tRNAs, including tRNA<jats:sup>Lys3</jats:sup> and tRNA<jats:sup>GlyGCC</jats:sup>, before binding to the plasma membrane, but the role of tRNA on assembly is poorly understood. The long‐term goal of this work is to study the MA:tRNA complex and elucidate its 3D structure as characterization of this interaction may shed light on the function of tRNA during membrane targeting. To achieve this goal, conditions to stabilize MA and the tRNA independently and in complex must be established. Nuclear magnetic resonance (NMR) and gel electrophoresis were employed to identify conditions that stabilized the tRNA and MA independently. Electrophoretic mobility shift assays (EMSAs) were carried out to probe MA:tRNA interactions under these conditions and showed complex formation upon addition of a stoichiometric ratio of MA to tRNA. This work lays a foundation to study thermodynamics of the MA‐tRNA interaction and determine the three‐dimensional structure of the complex.</jats:p></jats:sec><jats:sec><jats:title>Support or Funding Information</jats:title><jats:p>This research was sponsored by NIH/NIGMS MARC U*STAR T34 HHS 00026 National Research Service Award to UMBC, HHMI, and NIH grants R01GM042561 and 8R01AI50498.</jats:p></jats:sec>