7RDM

Crystal structure of PCDN-38B, a broadly neutralizing anti-HIV antibody

7RDM の概要

• エントリーDOI: 10.2210/pdb7rdm/pdb
• 関連するPDBエントリー: 7RDJ 7RDK 7RDL
• 分子名称: PCDN-38B Fab light chain, PCDN-38B Fab heavy chain, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: antibody, broadly neutralizing, hiv-1, cysteinylation, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50993.19

構造登録者

Omorodion, O.,Wilson, I.A. (登録日: 2021-07-09, 公開日: 2021-11-10, 最終更新日: 2024-10-23)

主引用文献

Omorodion, O.,Wilson, I.A.
Structural and Biochemical Characterization of Cysteinylation in Broadly Neutralizing Antibodies to HIV-1.
J.Mol.Biol., 433:167303-167303, 2021

PubMed Abstract: Antibodies with exceptional breadth and potency have been elicited in some individuals during natural HIV-1 infection. Elicitation and affinity maturation of broadly neutralizing antibodies (bnAbs) is therefore the central goal of HIV-1 vaccine development. The functional properties of bnAbs also make them attractive as immunotherapeutic agents, which has led to their production and optimization for passive immunotherapy. This process requires in vitro manufacturing and monitoring of any heterogeneous expression, especially when subpopulations of antibodies are produced with varying levels of biological activity. Post-translational modification (PTM) of antibodies can contribute to heterogeneity and is the focus of this study. Specifically, we have investigated cysteinylation in a bnAb lineage (PCDN family) targeting the N332-glycan supersite on the surface envelope glycoprotein (Env) of HIV-1. This PTM is defined by capping of unpaired cysteine residues with molecular cysteine. Through chromatography and mass spectrometry, we were able to characterize subpopulations of cysteinylated and non-cysteinylated antibodies when expressed in mammalian cells. The crystal structures of two PCDN antibodies represent the first structures of a cysteinylated antibody and reveal that the cysteinylation in this case is located in CDRH3. Biophysical studies indicate that cysteinylation of these HIV-1 antibodies does not interfere with antigen binding, which has been reported to occur in other cysteinylated antibodies. As such, these studies highlight the need for further investigation of cysteinylation in anti-HIV and other bnAbs.

PubMed: 34666044
DOI: 10.1016/j.jmb.2021.167303

実験手法

X-RAY DIFFRACTION (2.08 Å)