3UP1

Crystal structure of the unliganded human interleukin-7 receptor extracellular domain

3UP1 の概要

• エントリーDOI: 10.2210/pdb3up1/pdb
• 分子名称: Interleukin-7 receptor subunit alpha, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose, ... (7 entities in total)
• 機能のキーワード: cytokine receptor, fibronectin type 3 fold, membrane and soluble, glycosylation, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53629.05

構造登録者

McElroy, C.A.,Holland, P.J.,Walsh, S.T.R. (登録日: 2011-11-17, 公開日: 2012-02-08, 最終更新日: 2024-10-30)

主引用文献

McElroy, C.A.,Holland, P.J.,Zhao, P.,Lim, J.M.,Wells, L.,Eisenstein, E.,Walsh, S.T.
Structural reorganization of the interleukin-7 signaling complex.
Proc.Natl.Acad.Sci.USA, 109:2503-2508, 2012

PubMed Abstract: We report here an unliganded receptor structure in the common gamma-chain (γ(c)) family of receptors and cytokines. The crystal structure of the unliganded form of the interleukin-7 alpha receptor (IL-7Rα) extracellular domain (ECD) at 2.15 Å resolution reveals a homodimer forming an "X" geometry looking down onto the cell surface with the C termini of the two chains separated by 110 Å and the dimer interface comprising residues critical for IL-7 binding. Further biophysical studies indicate a weak association of the IL-7Rα ECDs but a stronger association between the γ(c)/IL-7Rα ECDs, similar to previous studies of the full-length receptors on CD4(+) T cells. Based on these and previous results, we propose a molecular mechanism detailing the progression from the inactive IL-7Rα homodimer and IL-7Rα-γ(c) heterodimer to the active IL-7-IL-7Rα-γ(c) ternary complex whereby the two receptors undergo at least a 90° rotation away from the cell surface, moving the C termini of IL-7Rα and γ(c) from a distance of 110 Å to less than 30 Å at the cell surface. This molecular mechanism can be used to explain recently discovered IL-7- and γ(c)-independent gain-of-function mutations in IL-7Rα from B- and T-cell acute lymphoblastic leukemia patients. The mechanism may also be applicable to other γ(c) receptors that form inactive homodimers and heterodimers independent of their cytokines.

PubMed: 22308406
DOI: 10.1073/pnas.1116582109

実験手法

X-RAY DIFFRACTION (2.15 Å)