4Z8M

Crystal structure of the MAVS-TRAF6 complex

4Z8M の概要

• エントリーDOI: 10.2210/pdb4z8m/pdb
• 分子名称: TNF receptor-associated factor 6, Peptide from Mitochondrial antiviral-signaling protein (2 entities in total)
• 機能のキーワード: complex, adaptor, e3 ligase, antiviral signaling, ligase-signaling protein complex, ligase/signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q9Y4K3; Mitochondrion outer membrane: Q7Z434
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43663.90

構造登録者

Shi, Z.B.,Zhou, Z. (登録日: 2015-04-09, 公開日: 2015-09-23, 最終更新日: 2023-11-08)

主引用文献

Shi, Z.,Zhang, Z.,Zhang, Z.,Wang, Y.,Li, C.,Wang, X.,He, F.,Sun, L.,Jiao, S.,Shi, W.,Zhou, Z.
Structural Insights into Mitochondrial Antiviral Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Signaling
J.Biol.Chem., 290:26811-26820, 2015

PubMed Abstract: In response to viral infection, cytosolic retinoic acid-inducible gene I-like receptors sense viral RNA and promote oligomerization of mitochondrial antiviral signaling protein (MAVS), which then recruits tumor necrosis factor receptor-associated factor (TRAF) family proteins, including TRAF6, to activate an antiviral response. Currently, the interaction between MAVS and TRAF6 is only partially understood, and atomic details are lacking. Here, we demonstrated that MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2 (T6BM2; amino acids 455-460). Further, we solved the crystal structure of MAVS T6BM2 in complex with the TRAF6 TRAF_C domain at 2.95 Å resolution. T6BM2 of MAVS binds to the canonical adaptor-binding groove of the TRAF_C domain. Structure-directed mutational analyses in vitro and in cells revealed that MAVS binding to TRAF6 via T6BM2 instead of T6BM1 is essential but not sufficient for an optimal antiviral response. Particularly, a MAVS mutant Y460E retained its TRAF6-binding ability as predicted but showed significantly impaired signaling activity, highlighting the functional importance of this tyrosine. Moreover, these observations were further confirmed in MAVS(-/-) mouse embryonic fibroblast cells. Collectively, our work provides a structural basis for understanding the MAVS-TRAF6 antiviral response.

PubMed: 26385923
DOI: 10.1074/jbc.M115.666578

実験手法

X-RAY DIFFRACTION (2.95 Å)