<br>设计不含共价 gp120-gp41 键的可溶性 HIV-1 包膜三聚体，具有普遍的天然样构象,Cell Reports

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设计不含共价 gp120-gp41 键的可溶性 HIV-1 包膜三聚体，具有普遍的天然样构象
Cell Reports ( IF 7.5 ) Pub Date : 2024-07-18 , DOI: 10.1016/j.celrep.2024.114518
Peng Zhang ₁ , Jason Gorman ₂ , Yaroslav Tsybovsky ₃ , Maolin Lu ₄ , Qingbo Liu ₅ , Vinay Gopan ₁ , Mamta Singh ₁ , Yin Lin ₁ , Huiyi Miao ₁ , Yuna Seo ₁ , Alice Kwon ₁ , Adam S Olia ₆ , Gwo-Yu Chuang ₆ , Hui Geng ₆ , Yen-Ting Lai ₆ , Tongqing Zhou ₆ , John R Mascola ₇ , Walther Mothes ₈ , Peter D Kwong ₆ , Paolo Lusso ₁

Affiliation

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Department of Cellular and Molecular Biology, School of Medicine, University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; School of Life Science and Technology, Southeast University, Nanjing 210096, China.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; ModeX Therapeutics, 20 Riverside Road, Weston, MA 02493, USA.
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

可溶性 HIV-1 包膜（Env）三聚体可作为有效的疫苗免疫原。广泛使用的 SOSIP 三聚体对于结构研究至关重要，但它们在 gp120 和 gp41 之间具有的二硫键限制了亚基间的迁移性，并可能改变抗原性。在这里，我们报道了一种替代策略，以产生不含共价 gp120-gp41 键的稳定可溶性 Env 三聚体。通过在 gp120 的内结构域和外结构域之间引入亚基内二硫键来实现稳定，定义为结构域间锁（IDL）。为不同分支的 HIV-1 Envs 产生显示天然样抗原谱的正确折叠 IDL 三聚体。重要的是，IDL 设计消除了 CD4 结合，同时不影响对 CD4 结合位点的有效中和抗体的识别。通过冷冻电子显微镜，IDL 三聚体显示采用封闭的预融合构型，而单分子荧光共振能量转移记录了天然样构象的高普遍性。因此，IDL 三聚体可能是有希望的疫苗免疫原候选者。

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更新日期：2024-07-18

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