4N0U

Ternary complex between Neonatal Fc receptor, serum albumin and Fc

4N0U の概要

• エントリーDOI: 10.2210/pdb4n0u/pdb
• 関連するPDBエントリー: 1AO6 1EXU 3FJT 4N0F
• 分子名称: IgG receptor FcRn large subunit p51, Beta-2-microglobulin, Serum albumin, ... (5 entities in total)
• 機能のキーワード: alpha/beta, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132795.42

構造登録者

Oganesyan, V.,Wu, H.,Dall'Acqua, W.F. (登録日: 2013-10-02, 公開日: 2014-02-05, 最終更新日: 2024-10-30)

主引用文献

Oganesyan, V.,Damschroder, M.M.,Cook, K.E.,Li, Q.,Gao, C.,Wu, H.,Dall'acqua, W.F.
Structural Insights into Neonatal Fc Receptor-based Recycling Mechanisms.
J.Biol.Chem., 289:7812-7824, 2014

PubMed Abstract: We report the three-dimensional structure of human neonatal Fc receptor (FcRn) bound concurrently to its two known ligands. More particularly, we solved the crystal structure of the complex between human FcRn, wild-type human serum albumin (HSA), and a human Fc engineered for improved pharmacokinetics properties (Fc-YTE). The crystal structure of human FcRn bound to wild-type HSA alone is also presented. HSA domain III exhibits an extensive interface of contact with FcRn, whereas domain I plays a lesser role. A molecular explanation for the HSA recycling mechanism is provided with the identification of FcRn His(161) as the only potential direct contributor to the corresponding pH-dependent process. At last, this study also allows an accurate structural definition of residues considered for decades as important to the human IgG/FcRn interaction and reveals Fc His(310) as a significant contributor to pH-dependent binding. Finally, we explain various structural mechanisms by which several Fc mutations (including YTE) result in increased human IgG binding to FcRn. Our study provides an unprecedented relevant understanding of the molecular basis of human Fc interaction with human FcRn.

PubMed: 24469444
DOI: 10.1074/jbc.M113.537563

実験手法

X-RAY DIFFRACTION (3.8 Å)