4NKQ

Structure of a Cytokine Receptor Complex

「3CXE」から置き換えられました

4NKQ の概要

• エントリーDOI: 10.2210/pdb4nkq/pdb
• 関連するPDBエントリー: 3cxe
• 分子名称: Cytokine receptor common subunit beta, Granulocyte-macrophage colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor receptor subunit alpha, ... (4 entities in total)
• 機能のキーワード: gm-csf, receptor complex, dodecamer, disease mutation, glycoprotein, membrane, phosphoprotein, transmembrane, cytokine, growth factor, secreted, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• 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: 97486.58

構造登録者

Parker, M.W.,Broughton, S.E. (登録日: 2013-11-13, 公開日: 2015-09-23, 最終更新日: 2024-10-30)

主引用文献

Broughton, S.E.,Hercus, T.R.,Nero, T.L.,Dottore, M.,McClure, B.J.,Dhagat, U.,Taing, H.,Gorman, M.A.,King-Scott, J.,Lopez, A.F.,Parker, M.W.
Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling.
Structure, 24:1271-1281, 2016

PubMed Abstract: The GM-CSF, IL-3, and IL-5 receptors constitute the βc family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:α subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures of both binary and ternary receptor complexes for the same cytokine. We have now solved the structure of the binary GM-CSF:GMRα complex at 2.8-Å resolution and compared it with the structure of the ternary complex, revealing distinct conformational changes. Guided by these differences we performed mutational and functional studies that, importantly, show GMRα interactions playing a major role in receptor signaling while βc interactions control high-affinity binding. These results support the notion that conformational changes underlie the mechanism of GM-CSF receptor activation and also suggest how related type I cytokine receptors signal.

PubMed: 27396825
DOI: 10.1016/j.str.2016.05.017

実験手法

X-RAY DIFFRACTION (3.301 Å)