9DMB
Rhesus RHA10.01 Fab in complex with HIV-1 Env BG505 DS-SOSIP trimer
Summary for 9DMB
| Entry DOI | 10.2210/pdb9dmb/pdb |
| EMDB information | 47000 |
| Descriptor | RHA10.01 Light chain, RHA10.01 Heavy chain, BG505 DS-SOSIP glycoprotein gp41, ... (8 entities in total) |
| Functional Keywords | cd4, hiv-1, shiv, t681, rhesus macaque, immune system |
| Biological source | Macaca mulatta More |
| Total number of polymer chains | 12 |
| Total formula weight | 391023.69 |
| Authors | Gorman, J.,Kwong, P.D. (deposition date: 2024-09-12, release date: 2025-06-18, Last modification date: 2025-06-25) |
| Primary citation | Morris, D.J.,Gorman, J.,Zhou, T.,Lora, J.,Connell, A.J.,Li, H.,Liu, W.,Roark, R.S.,Campion, M.S.,Carey, J.W.,Habib, R.,Li, Y.,Martella, C.L.,Park, Y.,Singh, A.,Sowers, K.J.,Teng, I.T.,Wang, S.,Chohan, N.,Ding, W.,Lauer, C.,Lewis, E.,Mason, R.D.,Rando, J.M.,Peyton, L.,Schramm, C.A.,Wagh, K.,Korber, B.,Seaman, M.S.,Douek, D.C.,Haynes, B.F.,Kulp, D.W.,Roederer, M.,Hahn, B.H.,Kwong, P.D.,Shaw, G.M. Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques. Cell Rep, 44:115848-115848, 2025 Cited by PubMed Abstract: Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first isolated RHA10, an infection-induced rhesus bNAb with 51% breadth. The cryoelectron microscopy (cryo-EM) structure of RHA10 with the HIV-1 envelope (Env) resembled prototypic human CD4bs bNAbs with CDR-H3-dominated binding. Env-antibody co-evolution revealed transient elimination of two Env CD4bs-proximal glycans near the time of RHA10-lineage initiation, and these glycan-deficient Envs bound preferentially to early RHA10 intermediates, suggesting that glycan deletions in infecting SHIVs could induce CD4bs bNAbs. To test this hypothesis, we constructed SHIV.CH505 variants with CD4bs-proximal glycan deletions. Infection of 11 macaques resulted in accelerated CD4bs bNAb responses in 9 compared with 1 of 115 control macaques. Glycan hole-based immunofocusing coupled to Env-Ab co-evolution can consistently induce broad CD4bs responses in macaques and serve as a model for HIV vaccine design. PubMed: 40516049DOI: 10.1016/j.celrep.2025.115848 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.27 Å) |
Structure validation
Download full validation report
