7C94

Crystal structure of the anti-human podoplanin antibody Fab fragment complex with glycopeptide

7C94 の概要

• エントリーDOI: 10.2210/pdb7c94/pdb
• 分子名称: Light chain of Fab fragment, Heavy chain of Fab fragment, Peptide from Podoplanin, ... (7 entities in total)
• 機能のキーワード: human podoplanin, monoclonal antibody, glycopeptide, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 103538.54

構造登録者

Suzuki, K.,Nakamura, S.,Ogasawara, S.,Naruchi, K.,Shimabukuro, J.,Tukahara, N.,Kaneko, M.K.,Kato, Y.,Murata, T. (登録日: 2020-06-04, 公開日: 2020-09-30, 最終更新日: 2023-11-29)

主引用文献

Ogasawara, S.,Suzuki, K.,Naruchi, K.,Nakamura, S.,Shimabukuro, J.,Tsukahara, N.,Kaneko, M.K.,Kato, Y.,Murata, T.
Crystal structure of an anti-podoplanin antibody bound to a disialylated O-linked glycopeptide.
Biochem.Biophys.Res.Commun., 533:57-63, 2020

PubMed Abstract: Podoplanin (PDPN) is a highly O-glycosylated glycoprotein that is utilized as a specific lymphatic endothelial marker under pathophysiological conditions. We previously developed an anti-human PDPN (hPDPN) monoclonal antibody (mAb), clone LpMab-3, which recognizes the epitope, including both the peptides and the attached disialy-core-l (NeuAcα2-3Galβl-3 [NeuAcα2-6]GalNAcαl-O-Thr) structure at the Thr76 residue in hPDPN. However, it is unclear if the mAb binds directly to both the peptides and glycans. In this study, we synthesized the binding epitope region of LpMab-3 that includes the peptide (-LVATSVNSV-T-GIRIEDLP-) possessing a disialyl-core-1 O-glycan at Thr76, and we determined the crystal structure of the LpMab-3 Fab fragment that was bound to the synthesized glycopeptide at a 2.8 Å resolution. The six amino acid residues and two sialic acid residues are directly associated with four complementarity-determining regions (CDRs; H1, H2, H3, and L3) and four CDRs (H2, H3, L1, and L3), respectively. These results suggest that IgG is advantageous for generating binders against spacious epitopes such as glycoconjugates.

PubMed: 32921414
DOI: 10.1016/j.bbrc.2020.08.103

実験手法

X-RAY DIFFRACTION (2.84 Å)