5MXA

Structure of unbound Interleukin-23

5MXA の概要

• エントリーDOI: 10.2210/pdb5mxa/pdb
• 分子名称: Interleukin-23 subunit alpha, Interleukin-12 subunit beta, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: cytokine, extracellular, inflammation, fibronectin type iii
• 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: 59827.50

構造登録者

Bloch, Y.,Savvides, S.N. (登録日: 2017-01-22, 公開日: 2017-12-20, 最終更新日: 2024-10-23)

主引用文献

Bloch, Y.,Bouchareychas, L.,Merceron, R.,Skladanowska, K.,Van den Bossche, L.,Detry, S.,Govindarajan, S.,Elewaut, D.,Haerynck, F.,Dullaers, M.,Adamopoulos, I.E.,Savvides, S.N.
Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12R beta 1.
Immunity, 48:45-58.e6, 2018

PubMed Abstract: Interleukin-23 (IL-23), an IL-12 family cytokine, plays pivotal roles in pro-inflammatory T helper 17 cell responses linked to autoimmune and inflammatory diseases. Despite intense therapeutic targeting, structural and mechanistic insights into receptor complexes mediated by IL-23, and by IL-12 family members in general, have remained elusive. We determined a crystal structure of human IL-23 in complex with its cognate receptor, IL-23R, and revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. The structural and functional hotspot of this interaction partially restructured the helical IL-23p19 subunit of IL-23 and restrained its IL-12p40 subunit to cooperatively bind the shared receptor IL-12Rβ1 with high affinity. Together with structural insights from the interaction of IL-23 with the inhibitory antibody briakinumab and by leveraging additional IL-23:antibody complexes, we propose a mechanistic paradigm for IL-23 and IL-12 whereby cognate receptor binding to the helical cytokine subunits primes recruitment of the shared receptors via the IL-12p40 subunit.

PubMed: 29287995
DOI: 10.1016/j.immuni.2017.12.008

実験手法

X-RAY DIFFRACTION (2.501 Å)