5UWC

Cytokine-receptor complex

5UWC の概要

• エントリーDOI: 10.2210/pdb5uwc/pdb
• 関連するPDBエントリー: 5UV8
• 分子名称: Interleukin-3 receptor subunit alpha, Interleukin-3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: cytokine, receptor, signalling, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48760.83

構造登録者

Broughton, S.E.,Parker, M.W. (登録日: 2017-02-21, 公開日: 2018-02-07, 最終更新日: 2024-11-06)

主引用文献

Broughton, S.E.,Hercus, T.R.,Nero, T.L.,Kan, W.L.,Barry, E.F.,Dottore, M.,Cheung Tung Shing, K.S.,Morton, C.J.,Dhagat, U.,Hardy, M.P.,Wilson, N.J.,Downton, M.T.,Schieber, C.,Hughes, T.P.,Lopez, A.F.,Parker, M.W.
A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.
Nat Commun, 9:386-386, 2018

PubMed Abstract: The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.

PubMed: 29374162
DOI: 10.1038/s41467-017-02633-7

実験手法

X-RAY DIFFRACTION (2.4 Å)