HIV-1 Env protein dynamics in cell membrane studied by Croft et al.

Check out two pre-publications available in bioRxiv, by lead-author Jacob Croft, from Kelly Lee's lab, at the University of Washington in collaboration with our Center’s Computational Biology Core scientists, Hung Do and S. Gnanakaran from Gnana's lab at Los Alamos National Laboratory.   Croft et al. used cryo-electron tomography and sub-tomogram averaging of HIV-1 virus-like particles (VLPs), Hydrogen/Deuterium-Exchange Mass Spectrometry and Molecular Dynamics to capture the structural dynamics of HIV-1 Env proteins in the context of the cell membrane. They identified critical interactions and Env structural rearrangements providing insight to essential roles the membrane plays in presenting the Envs in its native conformation on the virion surface and dig deeper in a follow-up paper, revealing critical interactions inside the cell, between the Env cytoplasmic tail and matrix domain of Gag polyprotein, required for Env assembly, presentation, clustering, receptor binding and membrane fusion, all essential for viral propagation.   These exciting results reveal the power of these synergistic approaches and the importance of studying Env structures in the context of a membrane. Inside the cell, Gag polyproteins ,recruited to the inner leaflet, help package and present the Env on the outside cell surface. The cell now poised to infect new cells while, simultaneously, exposing the Env to an unrelenting barrage of antibodies seeking to neutralize further infection. Paper #1 https://lnkd.in/eizZwbJF Follow-up Paper https://lnkd.in/exxQxax9

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