3ula

Crystal structure of the TV3 mutant F63W-MD-2-Eritoran complex

spinqualitylabelsall models 3ula, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ula is a 4 chain structure with sequence from Eptatretus burgeri and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.6Å Ligands: BMA, E55, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. Publication Abstract from PubMed Repeat proteins are increasingly attracting much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural features. Nonetheless, engineering interaction interface and understanding molecular basis for affinity maturation of repeat proteins still remain a challenge. Here, we present a structure-based rational design of a repeat protein with high binding affinity for a target protein. As a model repeat protein, a Toll-like receptor4 (TLR4) decoy receptor composed of leucine-rich repeat (LRR) modules was used, and its interaction interface was rationally engineered to increase the binding affinity for myeloid differentiation protein 2 (MD2). Based on the complex crystal structure of the decoy receptor with MD2, we first designed single amino acid substitutions in the decoy receptor, and obtained three variants showing a binding affinity (K(D)) one-order of magnitude higher than the wild-type decoy receptor. The interacting modes and contributions of individual residues were elucidated by analyzing the crystal structures of the single variants. To further increase the binding affinity, single positive mutations were combined, and two double mutants were shown to have about 3000- and 565-fold higher binding affinities than the wild-type decoy receptor. Molecular dynamics simulations and energetic analysis indicate that an additive effect by two mutations occurring at nearby modules was the major contributor to the remarkable increase in the binding affinities. Structure-based rational design of a Toll-like receptor 4 (TLR4) decoy receptor with high binding affinity for a target protein.,Han J, Kim HJ, Lee SC, Hong S, Park K, Jeon YH, Kim D, Cheong HK, Kim HS PLoS One. 2012;7(2):e30929. Epub 2012 Feb 17. PMID:22363519 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Toll-like Receptor 3D structures Variable lymphocyte receptor 3D structures

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