6MPH
Cryo-EM structure at 3.8 A resolution of HIV-1 fusion peptide-directed antibody, DF1W-a.01, elicited by vaccination of Rhesus macaques, in complex with stabilized HIV-1 Env BG505 DS-SOSIP, which was also bound to antibodies VRC03 and PGT122
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Summary for 6MPH
Entry DOI | 10.2210/pdb6mph/pdb |
EMDB information | 9189 |
Descriptor | DF1W-a.01 heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total) |
Functional Keywords | complex, fusion peptide, neutralizing antibody, hiv-1 envelope, viral protein |
Biological source | Macaca mulatta More |
Total number of polymer chains | 24 |
Total formula weight | 503183.86 |
Authors | Acharya, P.,Xu, K.,Kwong, P.D. (deposition date: 2018-10-06, release date: 2019-07-24, Last modification date: 2024-10-23) |
Primary citation | Kong, R.,Duan, H.,Sheng, Z.,Xu, K.,Acharya, P.,Chen, X.,Cheng, C.,Dingens, A.S.,Gorman, J.,Sastry, M.,Shen, C.H.,Zhang, B.,Zhou, T.,Chuang, G.Y.,Chao, C.W.,Gu, Y.,Jafari, A.J.,Louder, M.K.,O'Dell, S.,Rowshan, A.P.,Viox, E.G.,Wang, Y.,Choi, C.W.,Corcoran, M.M.,Corrigan, A.R.,Dandey, V.P.,Eng, E.T.,Geng, H.,Foulds, K.E.,Guo, Y.,Kwon, Y.D.,Lin, B.,Liu, K.,Mason, R.D.,Nason, M.C.,Ohr, T.Y.,Ou, L.,Rawi, R.,Sarfo, E.K.,Schon, A.,Todd, J.P.,Wang, S.,Wei, H.,Wu, W.,Mullikin, J.C.,Bailer, R.T.,Doria-Rose, N.A.,Karlsson Hedestam, G.B.,Scorpio, D.G.,Overbaugh, J.,Bloom, J.D.,Carragher, B.,Potter, C.S.,Shapiro, L.,Kwong, P.D.,Mascola, J.R. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. Cell, 178:567-584.e19, 2019 Cited by PubMed Abstract: The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization. PubMed: 31348886DOI: 10.1016/j.cell.2019.06.030 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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