PDBsum entry 4z8m

Ligase/signaling protein

PDB id: 4z8m

Contents

Protein chains

152 a.a.

Ligands

HIS-GLY-PRO-GLU-GLU-ASN-GLU-TYR-LYS

GLY-PRO-GLU-GLU-ASN-GLU-TYR

PDB id:

4z8m

Name:

Ligase/signaling protein

Title:

Crystal structure of the mavs-traf6 complex

Structure:

Tnf receptor-associated factor 6. Chain: a, b. Fragment: unp residues 346-504. Synonym: e3 ubiquitin-protein ligase traf6,interleukin-1 signal transducer,ring finger protein 85. Engineered: yes. Peptide from mitochondrial antiviral-signaling protein. Chain: c, d. Fragment: unp residues 450-468.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: traf6, rnf85. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: condonplus.

Resolution:

2.95Å R-factor: 0.192 R-free: 0.238

Authors:

Z.B.Shi,Z.Zhou

Key ref:

Z.Shi et al. (2015). Structural Insights into mitochondrial antiviral signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling. J Biol Chem, 290, 26811-26820. PubMed id: 26385923 DOI: 10.1074/jbc.M115.666578

Date:

09-Apr-15 Release date: 23-Sep-15

Protein chains

Q9Y4K3  (TRAF6_HUMAN) -  TNF receptor-associated factor 6 from Homo sapiens

Seq: 522 a.a.

Struc: 152 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1074/jbc.M115.666578

J Biol Chem 290:26811-26820 (2015)

PubMed id: 26385923

Structural Insights into mitochondrial antiviral signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling.

Z.Shi, Z.Zhang, Z.Zhang, Y.Wang, C.Li, X.Wang, F.He, L.Sun, S.Jiao, W.Shi, Z.Zhou.

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.