4DN5

Crystal Structure of NF-kB-inducing Kinase (NIK)

4DN5 の概要

• エントリーDOI: 10.2210/pdb4dn5/pdb
• 分子名称: Mitogen-activated protein kinase kinase kinase 14, MAGNESIUM ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: non-rd kinase, protein serine/threonine kinase, transferase, atp binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q99558
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79907.04

構造登録者

Min, X.,Liu, J.,Sudom, A.,Walker, N.P.,Wang, Z. (登録日: 2012-02-08, 公開日: 2012-06-27, 最終更新日: 2024-02-28)

主引用文献

Liu, J.,Sudom, A.,Min, X.,Cao, Z.,Gao, X.,Ayres, M.,Lee, F.,Cao, P.,Johnstone, S.,Plotnikova, O.,Walker, N.,Chen, G.,Wang, Z.
Structure of Nuclear Factor Kappa B-inducing kinase domain reveals a constitutively active conformation
J.Biol.Chem., 287:27326-27334, 2012

PubMed Abstract: NF-κB-inducing kinase (NIK) is a central component in the non-canonical NF-κB signaling pathway. Excessive NIK activity is implicated in various disorders, such as autoimmune conditions and cancers. Here, we report the first crystal structure of truncated human NIK in complex with adenosine 5'-O-(thiotriphosphate) at a resolution of 2.5 Å. This truncated protein is a catalytically active construct, including an N-terminal extension of 60 residues prior to the kinase domain, the kinase domain, and 20 residues afterward. The structure reveals that the NIK kinase domain assumes an active conformation in the absence of any phosphorylation. Analysis of the structure uncovers a unique role for the N-terminal extension sequence, which stabilizes helix αC in the active orientation and keeps the kinase domain in the catalytically competent conformation. Our findings shed light on the long-standing debate over whether NIK is a constitutively active kinase. They also provide a molecular basis for the recent observation of gain-of-function activity for an N-terminal deletion mutant (ΔN324) of NIK, leading to constitutive non-canonical NF-κB signaling with enhanced B-cell adhesion and apoptosis resistance.

PubMed: 22718757
DOI: 10.1074/jbc.M112.366658

実験手法

X-RAY DIFFRACTION (2.5 Å)