5H07

TNIP2-Ub complex, C2 form

Summary for 5H07

• Entry DOI: 10.2210/pdb5h07/pdb
• Descriptor: Polyubiquitin-C, TNFAIP3-interacting protein 2 (3 entities in total)
• Functional Keywords: coiled-coil, complex, signal transduction, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Ubiquitin: Cytoplasm : P0CG48; Cytoplasm : Q8NFZ5
• Total number of polymer chains: 3
• Total formula weight: 47128.51

Authors

Lo, Y.C.,Lin, S.C. (deposition date: 2016-10-04, release date: 2017-03-08, Last modification date: 2024-10-23)

Primary citation

Lin, S.M.,Lin, S.C.,Hong, J.Y.,Su, T.W.,Kuo, B.J.,Chang, W.H.,Tu, Y.F.,Lo, Y.C.
Structural Insights into Linear Tri-ubiquitin Recognition by A20-Binding Inhibitor of NF-kappa B, ABIN-2
Structure, 25:66-78, 2017

PubMed Abstract: Recognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-κB (NF-κB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-κB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration. Surprisingly, three ubiquitin units could form a right-handed helical trimer to bridge two ABIN2 dimers. The residues around the M1-linkage are crucial for ABIN2 to recognize tri-ubiquitin. The tri-ubiquitin bridging two ABIN2 dimers model suggests a possible higher-order signaling complex assembled between M1-linked polyubiquitinated proteins, ubiquitin-binding proteins, and effector signaling proteins in signal transduction.

PubMed: 27916521
DOI: 10.1016/j.str.2016.11.005

Experimental method

X-RAY DIFFRACTION (2.586 Å)