9Q0W
Cryo-EM Structure of HIV-1 BG505DS-SOSIP.664 Env Trimer Bound to DFPH-a.01_10R59P_LC Fab
This is a non-PDB format compatible entry.
Summary for 9Q0W
| Entry DOI | 10.2210/pdb9q0w/pdb |
| EMDB information | 72108 |
| Descriptor | HIV-1 BG505 DS-SOSIP gp120, BG505 DS-SOSIP GP41, DFPH-a.01_10R59P_LC Fab heavy chain, ... (7 entities in total) |
| Functional Keywords | antibody improvement, broadly neutralizing antibody, epitope, fusion peptide, hiv-1 vaccine, paratope, viral protein |
| Biological source | Human immunodeficiency virus 1 More |
| Total number of polymer chains | 12 |
| Total formula weight | 376299.07 |
| Authors | |
| Primary citation | Franca, C.T.,Pletnev, S.,Madan, B.,Katsamba, P.S.,McKee, K.,Morano, N.C.,Zhang, B.,Bahna, F.,Bylund, T.,Lin, B.C.,Louder, M.K.,Mannepalli, S.,Nimrania, R.,O'Dell, S.,Doria-Rose, N.A.,Kwong, P.D.,Shapiro, L.,Sheng, Z.,Zhou, T.,DeKosky, B.J. Yeast Display Reveals Plentiful Mutations That Improve Fusion Peptide Vaccine-Elicited Antibodies Beyond 59% HIV-1 Neutralization Breadth. Vaccines (Basel), 13:-, 2025 Cited by PubMed Abstract: : Vaccine elicitation of antibodies with high HIV-1 neutralization breadth is a long-standing goal. Recently, the induction of such antibodies has been achieved at the fusion peptide site of vulnerability. Questions remain, however, as to how much anti-fusion peptide antibodies can be improved and whether their neutralization breadth and potency are sufficient to prevent HIV-1 infection. : Here, we use yeast display coupled with deep mutational screening and biochemical and structural analyses to study the improvement of the best fusion peptide-directed, vaccine-elicited antibody, DFPH_a.01, with an initial 59% breadth. : Yeast display identified both single and double mutations that improved recognition of HIV-1 envelope trimers. We characterized two paratope-distal light chain (LC) mutations, S10R and S59P, which together increased breadth to 63%. Biochemical analysis demonstrated DFPH-a.01_10R59P-LC, and its component mutations, to have increased affinity and stability. Cryo-EM structural analysis revealed elbow-angle influencing by S10R-LC and isosteric positioning by S59P-LC as explanations for enhanced breadth, affinity, and stability. : These results, along with another antibody with enhanced performance (DFPH-a.01_1G10A56K-LC with 64% breadth), suggest that mutations improving DFPH_a.01 are plentiful, an important vaccine insight. PubMed: 41295471DOI: 10.3390/vaccines13111098 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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