5DK3

Crystal Structure of Pembrolizumab, a full length IgG4 antibody

5DK3 の概要

• エントリーDOI: 10.2210/pdb5dk3/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900003
• 分子名称: Light Chain, Heavy Chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-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, ... (7 entities in total)
• 機能のキーワード: cancer, antibody, subclasses, igg4, melanoma, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 149953.56

構造登録者

Scapin, G.,Prosise, W.,Reichert, P. (登録日: 2015-09-02, 公開日: 2015-11-18, 最終更新日: 2024-11-13)

主引用文献

Scapin, G.,Yang, X.,Prosise, W.W.,McCoy, M.,Reichert, P.,Johnston, J.M.,Kashi, R.S.,Strickland, C.
Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab.
Nat.Struct.Mol.Biol., 22:953-958, 2015

PubMed Abstract: Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc domain is glycosylated at the CH2 domain on both chains, but one CH2 domain is rotated 120° with respect to the conformation observed in all reported structures to date, and its glycan chain faces the solvent. We speculate that this new conformation is driven by the shorter hinge. The structure suggests a role for the S228P mutation in preventing the IgG4 arm exchange. In addition, this unusual Fc conformation suggests possible structural diversity between IgG subclasses and shows that use of isolated antibody fragments could mask potentially important interactions, owing to molecular flexibility.

PubMed: 26595420
DOI: 10.1038/nsmb.3129

実験手法

X-RAY DIFFRACTION (2.28 Å)