8fad › Citations

Asymmetric conformations of cleaved HIV-1 envelope glycoprotein trimers in styrene-maleic acid lipid nanoparticles.

<div class='caption-title'>Asymmetric structures of the AD8 and AE2 Env trimers.</div>
<div class='caption-title'>Comparison of Env protomer conformations.</div>
<div class='caption-title'>Comparison of trimer geometry among different Env structures.</div>
Wang K, Zhang S, Go EP, Ding H, Wang WL, Nguyen HT, Kappes JC, Desaire H, Sodroski J, Mao Y
OpenAccess logo Commun Biol 6 535 (2023)
Cited: 6 times
EuropePMC logo PMID: 37202420

Abstract

During virus entry, the pretriggered human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer initially transits into a default intermediate state (DIS) that remains structurally uncharacterized. Here, we present cryo-EM structures at near-atomic resolution of two cleaved full-length HIV-1 Env trimers purified from cell membranes in styrene-maleic acid lipid nanoparticles without antibodies or receptors. The cleaved Env trimers exhibited tighter subunit packing than uncleaved trimers. Cleaved and uncleaved Env trimers assumed remarkably consistent yet distinct asymmetric conformations, with one smaller and two larger opening angles. Breaking conformational symmetry is allosterically coupled with dynamic helical transformations of the gp41 N-terminal heptad repeat (HR1N) regions in two protomers and with trimer tilting in the membrane. The broken symmetry of the DIS potentially assists Env binding to two CD4 receptors-while resisting antibody binding-and promotes extension of the gp41 HR1 helical coiled-coil, which relocates the fusion peptide closer to the target cell membrane.

Articles - 8fad mentioned but not cited (2)

  1. Alternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan. Jeffy J, Parthasarathy D, Ahmed S, Cervera-Benet H, Xiong U, Harris M, Mazurov D, Pickthorn S, Herschhorn A. mBio 15 e0268623 (2024)
  2. research-article Alternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan. Jeffy J, Parthasarathy D, Ahmed S, Cervera-Benet H, Xiong U, Harris M, Mazurov D, Pickthorn S, Herschhorn A. bioRxiv 2023.11.20.567910 (2023)


Reviews citing this publication (1)

  1. Progress with induction of HIV broadly neutralizing antibodies in the Duke Consortia for HIV/AIDS Vaccine Development. Haynes BF, Wiehe K, Alam SM, Weissman D, Saunders KO. Curr Opin HIV AIDS 18 300-308 (2023)

Articles citing this publication (3)

  1. Alterations in gp120 glycans or the gp41 fusion peptide-proximal region modulate the stability of the human immunodeficiency virus (HIV-1) envelope glycoprotein pretriggered conformation. Zhang Z, Wang Q, Nguyen HT, Chen HC, Chiu TJ, Smith Iii AB, Sodroski JG. J Virol 97 e0059223 (2023)
  2. Conformations of Human Immunodeficiency Virus Envelope Glycoproteins in Detergents and Styrene-Maleic Acid Lipid Particles. Zhou R, Zhang S, Nguyen HT, Ding H, Gaffney A, Kappes JC, Smith AB, Sodroski JG. J Virol 97 e0032723 (2023)
  3. Membrane HIV-1 envelope glycoproteins stabilized more strongly in a pretriggered conformation than natural virus Envs. Zhang Z, Anang S, Nguyen HT, Fritschi C, Smith AB, Sodroski JG. iScience 27 110141 (2024)


Quick links