5ijb

The ligand-free structure of the mouse TLR4/MD-2 complex

spinqualitylabelsall models 5ijb, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ijb is a 4 chain structure with sequence from Eptatretus burgeri and Mus musculus. This structure supersedes the now removed PDB entry 5hg3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.91Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TLR4_MOUSE Note=The protein is encoded by the Lps locus, an important susceptibility locus, influencing the propensity to develop a disseminated Gram-negative infection. Function Q4G1L2_EPTBU TLR4_MOUSE Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity). Publication Abstract from PubMed Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-A resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS. TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.,Wang Y, Su L, Morin MD, Jones BT, Whitby LR, Surakattula MM, Huang H, Shi H, Choi JH, Wang KW, Moresco EM, Berger M, Zhan X, Zhang H, Boger DL, Beutler B Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E884-93. doi:, 10.1073/pnas.1525639113. Epub 2016 Feb 1. PMID:26831104 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Variable lymphocyte receptor 3D structures

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