6CK9
Crystal Structure of HIV-1 ConC_Base0 Prefusion Env Trimer in Complex with Human Antibody Fragment 3H109L and 35O22 variants at 3.5 Angstrom
Summary for 6CK9
| Entry DOI | 10.2210/pdb6ck9/pdb |
| Descriptor | gp41 ectodomain of 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-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total) |
| Functional Keywords | hiv-1 envelope fusion glycoprotein, viral protein |
| Biological source | Human immunodeficiency virus 1 More |
| Total number of polymer chains | 6 |
| Total formula weight | 155614.33 |
| Authors | Lai, Y.-T.,Kwong, P.D. (deposition date: 2018-02-27, release date: 2018-04-25, Last modification date: 2024-10-30) |
| Primary citation | Rutten, L.,Lai, Y.T.,Blokland, S.,Truan, D.,Bisschop, I.J.M.,Strokappe, N.M.,Koornneef, A.,van Manen, D.,Chuang, G.Y.,Farney, S.K.,Schuitemaker, H.,Kwong, P.D.,Langedijk, J.P.M. A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers. Cell Rep, 23:584-595, 2018 Cited by PubMed Abstract: The heavily glycosylated native-like envelope (Env) trimer of HIV-1 is expected to have low immunogenicity, whereas misfolded forms are often highly immunogenic. High-quality correctly folded Envs may therefore be critical for developing a vaccine that induces broadly neutralizing antibodies. Moreover, the high variability of Env may require immunizations with multiple Envs. Here, we report a universal strategy that provides for correctly folded Env trimers of high quality and yield through a repair-and-stabilize approach. In the repair stage, we utilized a consensus strategy that substituted rare strain-specific residues with more prevalent ones. The stabilization stage involved structure-based design and experimental assessment confirmed by crystallographic feedback. Regions important for the refolding of Env were targeted for stabilization. Notably, the α9-helix and an intersubunit β sheet proved to be critical for trimer stability. Our approach provides a means to produce prefusion-closed Env trimers from diverse HIV-1 strains, a substantial advance for vaccine development. PubMed: 29642014DOI: 10.1016/j.celrep.2018.03.061 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.714 Å) |
Structure validation
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