3fxi
Crystal structure of the human TLR4-human MD-2-E.coli LPS Ra complexCrystal structure of the human TLR4-human MD-2-E.coli LPS Ra complex
DiseaseDisease
[TLR4_HUMAN] Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM:611488]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
FunctionFunction
[TLR4_HUMAN] 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. Also involved in LPS-independent inflammatory responses triggered by Ni(2+). These responses require non-conserved histidines and are, therefore, species-specific.[1] [LY96_HUMAN] Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both MD2 and TLR4, but not TLR4 alone, respond to LPS.
About this StructureAbout this Structure
3fxi is a 4 chain structure with sequence from Escherichia coli and Homo sapiens. The November 2011 RCSB PDB Molecule of the Month feature on Toll-like Receptors by David Goodsell is 10.2210/rcsb_pdb/mom_2011_11. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. 2009 Apr 30;458(7242):1191-5. Epub 2009 Mar 1. PMID:19252480 doi:10.1038/nature07830
- ↑ Lin SC, Lo YC, Wu H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature. 2010 Jun 17;465(7300):885-90. Epub 2010 May 19. PMID:20485341 doi:10.1038/nature09121
- ↑ Schmidt M, Raghavan B, Muller V, Vogl T, Fejer G, Tchaptchet S, Keck S, Kalis C, Nielsen PJ, Galanos C, Roth J, Skerra A, Martin SF, Freudenberg MA, Goebeler M. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol. 2010 Sep;11(9):814-9. doi: 10.1038/ni.1919. Epub 2010 Aug 15. PMID:20711192 doi:10.1038/ni.1919