5TPP

Crystal Structure of DH270.5 (unliganded) from the DH270 Broadly Neutralizing N332-glycan Dependent Lineage

Summary for 5TPP

• Entry DOI: 10.2210/pdb5tpp/pdb
• Related: 5TPL 5TQA 5TRP 5U0R 5U0U 5U15
• EMDB information: 8507
• Descriptor: DH270.5 Fab heavy chain, DH270.5 Fab light chain, SODIUM ION, ... (5 entities in total)
• Functional Keywords: fab fragment, hiv-1, antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48868.27

Authors

Fera, D.,Harrison, S.C. (deposition date: 2016-10-20, release date: 2017-03-15, Last modification date: 2024-10-23)

Primary citation

Bonsignori, M.,Kreider, E.F.,Fera, D.,Meyerhoff, R.R.,Bradley, T.,Wiehe, K.,Alam, S.M.,Aussedat, B.,Walkowicz, W.E.,Hwang, K.K.,Saunders, K.O.,Zhang, R.,Gladden, M.A.,Monroe, A.,Kumar, A.,Xia, S.M.,Cooper, M.,Louder, M.K.,McKee, K.,Bailer, R.T.,Pier, B.W.,Jette, C.A.,Kelsoe, G.,Williams, W.B.,Morris, L.,Kappes, J.,Wagh, K.,Kamanga, G.,Cohen, M.S.,Hraber, P.T.,Montefiori, D.C.,Trama, A.,Liao, H.X.,Kepler, T.B.,Moody, M.A.,Gao, F.,Danishefsky, S.J.,Mascola, J.R.,Shaw, G.M.,Hahn, B.H.,Harrison, S.C.,Korber, B.T.,Haynes, B.F.
Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.
Sci Transl Med, 9:-, 2017

PubMed Abstract: A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.

PubMed: 28298420
DOI: 10.1126/scitranslmed.aai7514

Experimental method

X-RAY DIFFRACTION (1.85 Å)