Structural Insights into Linear Tri-ubiquitin Recognition by A20-Binding Inhibitor of NF-κB, ABIN-2

Shan Meng Lin, Su Chang Lin, Jhen Yi Hong, Tsung Wei Su, Bai Jiun Kuo, Wei Hsin Chang, Yi Fan Tu, Yu Chih Lo

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)66-78
Number of pages13
Issue number1
Publication statusPublished - 2017 Jan 3

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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