5HN1

Crystal structure of Interleukin-37

5HN1 の概要

• エントリーDOI: 10.2210/pdb5hn1/pdb
• 分子名称: Interleukin-37, SULFATE ION (3 entities in total)
• 機能のキーワード: interleukin-1 cytokine inflammation interleukin-18, cytokine
• 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: 39426.92

構造登録者

Ellisdon, A.M.,Nold-Petry, C.A.,Nold, M.F.,Whisstock, J.C. (登録日: 2016-01-17, 公開日: 2017-02-22, 最終更新日: 2023-09-27)

主引用文献

Ellisdon, A.M.,Nold-Petry, C.A.,D'Andrea, L.,Cho, S.X.,Lao, J.C.,Rudloff, I.,Ngo, D.,Lo, C.Y.,Soares da Costa, T.P.,Perugini, M.A.,Conroy, P.J.,Whisstock, J.C.,Nold, M.F.
Homodimerization attenuates the anti-inflammatory activity of interleukin-37.
Sci Immunol, 2:-, 2017

PubMed Abstract: Dysregulation of the inflammatory response underlies numerous diseases. Although most interleukin-1 family cytokines are proinflammatory, human interleukin-37 (IL-37) is a powerful, broad-spectrum inhibitor of inflammation and immunity. We determined the crystal structure of IL-37 to establish the anti-inflammatory mechanism of this key cytokine in view of developing IL-37-based therapies. We found that two β-trefoil fold IL-37 molecules form a head-to-head dimer that is stable in solution. IL-37 variants mutated to convert the cytokine into an obligate monomer were up to 13-fold more effective than the dimer in suppressing proinflammatory events both in primary human blood cells and in vivo in murine endotoxic shock. Therapeutic exploitation of the powerful anti-inflammatory properties of monomeric IL-37 may prove beneficial in treating a wide range of inflammatory and autoimmune disorders.

PubMed: 28783685
DOI: 10.1126/sciimmunol.aaj1548

実験手法

X-RAY DIFFRACTION (2.25 Å)