1LB5: Traf6-rank Complex

Citation:
Abstract
Tumour-necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is the only TRAF family member that participates in signal transduction of both the TNF receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily; it is important for adaptive immunity, innate immunity and bone homeostasis. Here we report crystal structures of TRAF6, alone and in complex with TRAF6-binding peptides from CD40 and TRANCE-R (also known as RANK), members of the TNFR superfamily, to gain insight into the mechanism by which TRAF6 mediates several signalling cascades. A 40 degrees difference in the directions of the bound peptides in TRAF6 and TRAF2 shows that there are marked structural differences between receptor recognition by TRAF6 and other TRAFs. The structural determinant of the petide TRAF6 interaction reveals a Pro-X-Glu-X-X-(aromatic/acidic residue) TRAF6-binding motif, which is present not only in CD40 and TRANCE-R but also in the three IRAK adapter kinases for IL-1R/TLR signalling. Cell-permeable peptides with the TRAF6-binding motif inhibit TRAF6 signalling, which indicates their potential as therapeutic modulators. Our studies identify a universal mechanism by which TRAF6 regulates several signalling cascades in adaptive immunity, innate immunity and bone homeostasis.
PDB ID: 1LB5Download
MMDB ID: 20223
PDB Deposition Date: 2002/4/2
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 1LB5: dimeric; determined by author and by software (PISA)
Molecular Components in 1LB5
Label Count Molecule
Proteins (2 molecules)
1
TNF Receptor-associated Factor 6(Gene symbol: TRAF6)
Molecule annotation
1
Receptor Activator of Nuclear Factor-kappa B(Gene symbol: TNFRSF11A)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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