5TPP

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

5TPP の概要

• エントリーDOI: 10.2210/pdb5tpp/pdb
• 関連するPDBエントリー: 5TPL 5TQA 5TRP 5U0R 5U0U 5U15
• EMDBエントリー: 8507
• 分子名称: DH270.5 Fab heavy chain, DH270.5 Fab light chain, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: fab fragment, hiv-1, antibody, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48868.27

構造登録者

Fera, D.,Harrison, S.C. (登録日: 2016-10-20, 公開日: 2017-03-15, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)