3QWR

Crystal structure of IL-23 in complex with an adnectin

3QWR の概要

• エントリーDOI: 10.2210/pdb3qwr/pdb
• 関連するPDBエントリー: 3QWQ
• 分子名称: Interleukin-12 subunit beta, Interleukin-23 subunit alpha, ADNECTIN, ... (5 entities in total)
• 機能のキーワード: four-helix bundle cytokine, ig domain, glycoprotein, immunoglobulin domain, secreted, antiviral defense, immune response, inflammatory response, innate immunity, tissue remodeling, adnectin, engineered binding protein, antibody mimic, protein binding-cytokine complex, protein binding/cytokine
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 66664.54

構造登録者

Wei, A.,Sheriff, S. (登録日: 2011-02-28, 公開日: 2012-02-01, 最終更新日: 2024-11-06)

主引用文献

Ramamurthy, V.,Krystek, S.R.,Bush, A.,Wei, A.,Emanuel, S.L.,Das Gupta, R.,Janjua, A.,Cheng, L.,Murdock, M.,Abramczyk, B.,Cohen, D.,Lin, Z.,Morin, P.,Davis, J.H.,Dabritz, M.,McLaughlin, D.C.,Russo, K.A.,Chao, G.,Wright, M.C.,Jenny, V.A.,Engle, L.J.,Furfine, E.,Sheriff, S.
Structures of adnectin/protein complexes reveal an expanded binding footprint.
Structure, 20:259-269, 2012

PubMed Abstract: Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin (¹⁰Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three ¹⁰Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23. Both Adnectins bind different epitopes than those bound by known monoclonal antibodies. Molecular modeling suggests that some of these epitopes might not be accessible to antibodies because of the size and concave shape of the antibody combining site. In addition to interactions from the Adnectin diversified loops, residues from the N terminus and/or the β strands interact with the target proteins in both complexes. Alanine-scanning mutagenesis confirmed the calculated binding energies of these β strand interactions, indicating that these nonloop residues can expand the available binding footprint.

PubMed: 22325775
DOI: 10.1016/j.str.2011.11.016

実験手法

X-RAY DIFFRACTION (3.25 Å)