6L9V

Crystal structure of mouse TIFA (T9D/C36S mutant)

6L9V の概要

• エントリーDOI: 10.2210/pdb6l9v/pdb
• 分子名称: TRAF-interacting protein with FHA domain-containing protein A (1 entity in total)
• 機能のキーワード: fha domain, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 90597.56

構造登録者

Nakamura, T.,Yamagata, Y. (登録日: 2019-11-11, 公開日: 2020-04-01, 最終更新日: 2023-11-22)

主引用文献

Nakamura, T.,Hashikawa, C.,Okabe, K.,Yokote, Y.,Chirifu, M.,Toma-Fukai, S.,Nakamura, N.,Matsuo, M.,Kamikariya, M.,Okamoto, Y.,Gohda, J.,Akiyama, T.,Semba, K.,Ikemizu, S.,Otsuka, M.,Inoue, J.I.,Yamagata, Y.
Structural analysis of TIFA: Insight into TIFA-dependent signal transduction in innate immunity.
Sci Rep, 10:5152-5152, 2020

PubMed Abstract: TRAF-interacting protein with a forkhead-associated (FHA) domain (TIFA), originally identified as an adaptor protein of TRAF6, has recently been shown to be involved in innate immunity, induced by a pathogen-associated molecular pattern (PAMP). ADP-β-D-manno-heptose, a newly identified PAMP, binds to alpha-kinase 1 (ALPK1) and activates its kinase activity to phosphorylate TIFA. Phosphorylation triggers TIFA oligomerisation and formation of a subsequent TIFA-TRAF6 oligomeric complex for ubiquitination of TRAF6, eventually leading to NF-κB activation. However, the structural basis of TIFA-dependent TRAF6 signalling, especially oligomer formation of the TIFA-TRAF6 complex remains unknown. In the present study, we determined the crystal structures of mouse TIFA and two TIFA mutants-Thr9 mutated to either Asp or Glu to mimic the phosphorylation state-to obtain the structural information for oligomer formation of the TIFA-TRAF6 complex. Crystal structures show the dimer formation of mouse TIFA to be similar to that of human TIFA, which was previously reported. This dimeric structure is consistent with the solution structure obtained from small angle X-ray scattering analysis. In addition to the structural analysis, we examined the molecular assembly of TIFA and the TIFA-TRAF6 complex by size-exclusion chromatography, and suggested a model for the TIFA-TRAF6 signalling complex.

PubMed: 32198460
DOI: 10.1038/s41598-020-61972-6

実験手法

X-RAY DIFFRACTION (3.05 Å)