7S7I

Crystal structure of Fab in complex with MICA alpha3 domain

7S7I の概要

• エントリーDOI: 10.2210/pdb7s7i/pdb
• 分子名称: MHC class I chain-related protein A, Fab heavy chain, Fab light chain, ... (6 entities in total)
• 機能のキーワード: immunoglobulin, checkpoint, antibody, complex, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 359110.35

構造登録者

Lee, P.S.,Strop, P. (登録日: 2021-09-16, 公開日: 2022-10-05, 最終更新日: 2024-11-13)

主引用文献

Hogan, J.M.,Lee, P.S.,Wong, S.C.,West, S.M.,Morishige, W.H.,Bee, C.,Tapia, G.C.,Rajpal, A.,Strop, P.,Dollinger, G.
Residue-Level Characterization of Antibody Binding Epitopes Using Carbene Chemical Footprinting.
Anal.Chem., 95:3922-3931, 2023

PubMed Abstract: Characterization of antibody binding epitopes is an important factor in therapeutic drug discovery, as the binding site determines and drives antibody pharmacology and pharmacokinetics. Here, we present a novel application of carbene chemical footprinting with mass spectrometry for identification of antibody binding epitopes at the single-residue level. Two different photoactivated diazirine reagents provide complementary labeling information allowing structural refinement of the antibody binding interface. We applied this technique to map the epitopes of multiple MICA and CTLA-4 antibodies and validated the findings with X-ray crystallography and yeast surface display epitope mapping. The characterized epitopes were used to understand biolayer interferometry-derived competitive binding results at the structural level. We show that carbene footprinting provides fast and high-resolution epitope information critical in the antibody selection process and enables mechanistic understanding of function to accelerate the drug discovery process.

PubMed: 36791402
DOI: 10.1021/acs.analchem.2c03091

実験手法

X-RAY DIFFRACTION (2.4 Å)