1lb6

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spinqualitylabelsall models 1lb6, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

TRAF6-CD40 Complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known disease associated with this structure: Immunodeficiency with hyper-IgM, type 3 OMIM:[109535]

About this Structure

1LB6 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Distinct molecular mechanism for initiating TRAF6 signalling., Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, Segal D, Dzivenu OK, Vologodskaia M, Yim M, Du K, Singh S, Pike JW, Darnay BG, Choi Y, Wu H, Nature. 2002 Jul 25;418(6896):443-7. PMID:12140561

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