7ZLK

AMC009 SOSIPv5.2 in complex with Fabs ACS114 and ACS122

7ZLK の概要

• エントリーDOI: 10.2210/pdb7zlk/pdb
• EMDBエントリー: 14783
• 分子名称: AMC009 SOSIPv5.2 envelope glycoprotein gp120, 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, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total)
• 機能のキーワード: hiv-1, antibodies, silent face, gp120-gp41 interface, viral protein
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 360729.83

構造登録者

van Schooten, J.,Ozorowski, G.,Ward, A. (登録日: 2022-04-15, 公開日: 2022-09-21, 最終更新日: 2025-07-02)

主引用文献

van Schooten, J.,Schorcht, A.,Farokhi, E.,Umotoy, J.C.,Gao, H.,van den Kerkhof, T.L.G.M.,Dorning, J.,Rijkhold Meesters, T.G.,van der Woude, P.,Burger, J.A.,Bijl, T.,Ghalaiyini, R.,Torrents de la Pena, A.,Turner, H.L.,Labranche, C.C.,Stanfield, R.L.,Sok, D.,Schuitemaker, H.,Montefiori, D.C.,Burton, D.R.,Ozorowski, G.,Seaman, M.S.,Wilson, I.A.,Sanders, R.W.,Ward, A.B.,van Gils, M.J.
Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer.
Plos Pathog., 18:e1010945-e1010945, 2022

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG+ B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient's remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses.

PubMed: 36395347
DOI: 10.1371/journal.ppat.1010945

実験手法

ELECTRON MICROSCOPY (3.99 Å)