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-Structure paper
Title | Design of soluble HIV-1 envelope trimers free of covalent gp120-gp41 bonds with prevalent native-like conformation. |
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Journal, issue, pages | Cell Rep, Vol. 43, Issue 8, Page 114518, Year 2024 |
Publish date | Jul 18, 2024 |
![]() | Peng Zhang / Jason Gorman / Yaroslav Tsybovsky / Maolin Lu / Qingbo Liu / Vinay Gopan / Mamta Singh / Yin Lin / Huiyi Miao / Yuna Seo / Alice Kwon / Adam S Olia / Gwo-Yu Chuang / Hui Geng / Yen-Ting Lai / Tongqing Zhou / John R Mascola / Walther Mothes / Peter D Kwong / Paolo Lusso / ![]() ![]() |
PubMed Abstract | Soluble HIV-1 envelope (Env) trimers may serve as effective vaccine immunogens. The widely utilized SOSIP trimers have been paramount for structural studies, but the disulfide bond they feature ...Soluble HIV-1 envelope (Env) trimers may serve as effective vaccine immunogens. The widely utilized SOSIP trimers have been paramount for structural studies, but the disulfide bond they feature between gp120 and gp41 constrains intersubunit mobility and may alter antigenicity. Here, we report an alternative strategy to generate stabilized soluble Env trimers free of covalent gp120-gp41 bonds. Stabilization was achieved by introducing an intrasubunit disulfide bond between the inner and outer domains of gp120, defined as interdomain lock (IDL). Correctly folded IDL trimers displaying a native-like antigenic profile were produced for HIV-1 Envs of different clades. Importantly, the IDL design abrogated CD4 binding while not affecting recognition by potent neutralizing antibodies to the CD4-binding site. By cryoelectron microscopy, IDL trimers were shown to adopt a closed prefusion configuration, while single-molecule fluorescence resonance energy transfer documented a high prevalence of native-like conformation. Thus, IDL trimers may be promising candidates as vaccine immunogens. |
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Methods | EM (single particle) |
Resolution | 3.3 - 4.5 Å |
Structure data | EMDB-44482, PDB-9ber: EMDB-44484, PDB-9bew: EMDB-44491, PDB-9bf6: |
Chemicals | ![]() ChemComp-NAG: ![]() ChemComp-SO4: ![]() ChemComp-PO4: |
Source |
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / CD4 / HIV-1 / SOSIP / Vaccine / gp120 / gp41 / VIRAL PROTEIN-IMMUNE SYSTEM complex |