5EP6

The crystal structure of NAP1 in complex with TBK1

5EP6 の概要

• エントリーDOI: 10.2210/pdb5ep6/pdb
• 分子名称: 5-azacytidine-induced protein 2, Serine/threonine-protein kinase TBK1, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: nap1, tbk1, calcoco2, protein binding-transferase complex, protein binding/transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q9H6S1 Q9UHD2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 24371.80

構造登録者

Li, F.,Xie, X.,Liu, J.,Pan, L. (登録日: 2015-11-11, 公開日: 2016-09-28, 最終更新日: 2024-03-20)

主引用文献

Li, F.,Xie, X.,Wang, Y.,Liu, J.,Cheng, X.,Guo, Y.,Gong, Y.,Hu, S.,Pan, L.
Structural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins.
Nat Commun, 7:12708-12708, 2016

PubMed Abstract: Optineurin is an important autophagy receptor involved in several selective autophagy processes, during which its function is regulated by TBK1. Mutations of optineurin and TBK1 are both associated with neurodegenerative diseases. However, the mechanistic basis underlying the specific interaction between optineurin and TBK1 is still elusive. Here we determine the crystal structures of optineurin/TBK1 complex and the related NAP1/TBK1 complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 interaction, and revealing a general binding mode between TBK1 and its associated adaptor proteins. In addition, we demonstrate that the glaucoma-associated optineurin E50K mutation not only enhances the interaction between optineurin and TBK1 but also alters the oligomeric state of optineurin, and the ALS-related TBK1 E696K mutation specifically disrupts the optineurin/TBK1 complex formation but has little effect on the NAP1/TBK1 complex. Thus, our study provides mechanistic insights into those currently known disease-causing optineurin and TBK1 mutations found in patients.

PubMed: 27620379
DOI: 10.1038/ncomms12708

実験手法

X-RAY DIFFRACTION (1.451 Å)