Summary for 8EU8
| Entry DOI | 10.2210/pdb8eu8/pdb |
| EMDB information | 28608 |
| Descriptor | CH848 10.17DT SOSIP Envelope glycoprotein gp160, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | hiv-1, env, viral fusion protein, glycoprotein, viral protein |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 3 |
| Total formula weight | 246697.04 |
| Authors | Wrapp, D.,Acharya, P.,Haynes, B.F. (deposition date: 2022-10-18, release date: 2023-01-04, Last modification date: 2024-10-09) |
| Primary citation | Wrapp, D.,Mu, Z.,Thakur, B.,Janowska, K.,Ajayi, O.,Barr, M.,Parks, R.,Mansouri, K.,Edwards, R.J.,Hahn, B.H.,Acharya, P.,Saunders, K.O.,Haynes, B.F. Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield. J.Virol., 97:e0167322-e0167322, 2023 Cited by PubMed Abstract: The envelope glycoprotein (Env) is the main focus of human immunodeficiency virus type 1 (HIV-1) vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expression due to their inherent metastability, making biochemical and immunological experiments impractical or impossible. Here, we report a novel proline stabilization strategy to facilitate the production of prefusion Env trimers. This approach, termed "2P," works synergistically with previously described SOSIP mutations and dramatically increases the yield of recombinantly expressed Env ectodomains without altering the antigenic or conformational properties of near-native Env. We determined that the 2P mutations function by enhancing the durability of the prefusion conformation and that this stabilization strategy is broadly applicable to evolutionarily and antigenically diverse Env constructs. These findings provide a new Env stabilization platform to facilitate biochemical research and expand the number of Env variants that can be developed as future HIV-1 vaccine candidates. Recent estimates have placed the number of new human immunodeficiency virus type 1 (HIV-1) infections at approximately 1.5 million per year, emphasizing the ongoing and urgent need for an effective vaccine. The envelope (Env) glycoprotein is the main focus of HIV-1 vaccine development, but, due to its inherent metastability, many Env variants are difficult to recombinantly express in the relatively large quantities that are required for biochemical studies and animal trials. Here, we describe a novel structure-based stabilization strategy that works synergistically with previously described SOSIP mutations to increase the yield of prefusion HIV-1 Env. PubMed: 36633409DOI: 10.1128/jvi.01673-22 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.73 Å) |
Structure validation
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