3qb7

Interleukin-4 mutant RGA bound to cytokine receptor common gamma

spinqualitylabelsall models 3qb7, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qb7 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.245Å Ligands: NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease IL4_HUMAN Genetic variations in IL4 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Function IL4_HUMAN Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Publication Abstract from PubMed Cytokines dimerize their receptors, with the binding of the 'second chain' triggering signaling. In the interleukin (IL)-4 and IL-13 system, different cell types express varying numbers of alternative second receptor chains (gammac or IL-13Ralpha1), forming functionally distinct type I or type II complexes. We manipulated the affinity and specificity of second chain recruitment by human IL-4. A type I receptor-selective IL-4 'superkine' with 3,700-fold higher affinity for gammac was three- to ten-fold more potent than wild-type IL-4. Conversely, a variant with high affinity for IL-13Ralpha1 more potently activated cells expressing the type II receptor and induced differentiation of dendritic cells from monocytes, implicating the type II receptor in this process. Superkines showed signaling advantages on cells with lower second chain numbers. Comparative transcriptional analysis reveals that the superkines induce largely redundant gene expression profiles. Variable second chain numbers can be exploited to redirect cytokines toward distinct cell subsets and elicit new actions, potentially improving the selectivity of cytokine therapy. Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines.,Junttila IS, Creusot RJ, Moraga I, Bates DL, Wong MT, Alonso MN, Suhoski MM, Lupardus P, Meier-Schellersheim M, Engleman EG, Utz PJ, Fathman CG, Paul WE, Garcia KC Nat Chem Biol. 2012 Oct 28. doi: 10.1038/nchembio.1096. PMID:23103943 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin 3D structures Interleukin receptor 3D structures

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