6VY2

Cryo-EM structure of M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer

6VY2 の概要

• エントリーDOI: 10.2210/pdb6vy2/pdb
• EMDBエントリー: 21456
• 分子名称: Glycoprotein 120, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: cryo-em, broadly neutralizing antibody, bnab, fab, human immunodeficiency virus, hiv-1, ch505, sosip, env, immune system
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 394729.68

構造登録者

Chan, K.-W.,Kong, X.P. (登録日: 2020-02-25, 公開日: 2020-05-06, 最終更新日: 2024-11-13)

主引用文献

Jia, M.,Liberatore, R.A.,Guo, Y.,Chan, K.W.,Pan, R.,Lu, H.,Waltari, E.,Mittler, E.,Chandran, K.,Finzi, A.,Kaufmann, D.E.,Seaman, M.S.,Ho, D.D.,Shapiro, L.,Sheng, Z.,Kong, X.P.,Bieniasz, P.D.,Wu, X.
VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA.
Cell Host Microbe, 27:963-, 2020

PubMed Abstract: The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.

PubMed: 32315598
DOI: 10.1016/j.chom.2020.03.024

実験手法

ELECTRON MICROSCOPY (4.86 Å)