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Structural basis of coreceptor recognition by HIV-1 envelope spike

Author

Listed:
  • Md Munan Shaik

    (Harvard Medical School
    Harvard Medical School)

  • Hanqin Peng

    (Harvard Medical School)

  • Jianming Lu

    (Codex BioSolutions
    Xiamen Amoytop Biotech)

  • Sophia Rits-Volloch

    (Harvard Medical School)

  • Chen Xu

    (University of Massachusetts Medical School)

  • Maofu Liao

    (Harvard Medical School)

  • Bing Chen

    (Harvard Medical School
    Harvard Medical School)

Abstract

HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160)3 cleaved to (gp120 and gp41)3, interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse viral and target-cell membranes. The gp120–coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3.9 Å resolution. The V3 loop of gp120 inserts into the chemokine-binding pocket formed by seven transmembrane helices of CCR5, and the N terminus of CCR5 contacts the CD4-induced bridging sheet of gp120. CCR5 induces no obvious allosteric changes in gp120 that can propagate to gp41; it does bring the Env trimer close to the target membrane. The N terminus of gp120, which is gripped by gp41 in the pre-fusion or CD4-bound Env, flips back in the CCR5-bound conformation and may irreversibly destabilize gp41 to initiate fusion. The coreceptor probably functions by stabilizing and anchoring the CD4-induced conformation of Env near the cell membrane. These results advance our understanding of HIV-1 entry into host cells and may guide the development of vaccines and therapeutic agents.

Suggested Citation

  • Md Munan Shaik & Hanqin Peng & Jianming Lu & Sophia Rits-Volloch & Chen Xu & Maofu Liao & Bing Chen, 2019. "Structural basis of coreceptor recognition by HIV-1 envelope spike," Nature, Nature, vol. 565(7739), pages 318-323, January.
    • Handle: RePEc:nat:nature:v:565:y:2019:i:7739:d:10.1038_s41586-018-0804-9
    DOI: 10.1038/s41586-018-0804-9
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    Cited by:

    1. Nikolas Friedrich & Emanuel Stiegeler & Matthias Glögl & Thomas Lemmin & Simon Hansen & Claus Kadelka & Yufan Wu & Patrick Ernst & Liridona Maliqi & Caio Foulkes & Mylène Morin & Mustafa Eroglu & Thom, 2021. "Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Shuang Yang & Giorgos Hiotis & Yi Wang & Junjian Chen & Jia-huai Wang & Mikyung Kim & Ellis L. Reinherz & Thomas Walz, 2022. "Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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