5EOA

Crystal structure of OPTN E50K mutant and TBK1 complex

Summary for 5EOA

• Entry DOI: 10.2210/pdb5eoa/pdb
• Related: 5EOF
• Descriptor: Optineurin, Serine/threonine-protein kinase TBK1 (3 entities in total)
• Functional Keywords: optineurin, tbk1, poag, als, protein binding-transferase complex, protein binding/transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, perinuclear region: Q96CV9; Cytoplasm : Q9UHD2
• Total number of polymer chains: 4
• Total formula weight: 31796.23

Authors

Li, F.,Xie, X.,Liu, J.,Pan, L. (deposition date: 2015-11-10, release date: 2016-09-28, Last modification date: 2024-03-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.503 Å)