5ur7

Crystal structure of engineered CCL20 disulfide locked dimer

spinqualitylabelsall models 5ur7, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ur7 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, IPA Gene: CCL20, LARC, MIP3A, SCYA20 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CCL20_HUMAN] Chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes. Inhibits proliferation of myeloid progenitors in colony formation assays. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. Possesses antibacterial activity E.coli ATCC 25922 and S.aureus ATCC 29213. Publication Abstract from PubMed Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, gammadelta T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds. A single-atom substitution yielded a CCL20 variant (CCL20 S64C) that acted as a partial agonist for the chemokine receptor CCR6. CCL20 S64C bound CCR6 and induced intracellular calcium release, consistent with G-protein activation, but exhibited minimal chemotactic activity. Instead, CCL20 S64C inhibited CCR6-mediated T cell migration with nominal impact on other chemokine receptor signaling. When given in an IL-23-dependent mouse model for psoriasis, CCL20 S64C prevented psoriatic inflammation and the up-regulation of IL-17A and IL-22. Our results validate CCR6 as a tractable therapeutic target for psoriasis and demonstrate the value of CCL20 S64C as a lead compound. Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model.,Getschman AE, Imai Y, Larsen O, Peterson FC, Wu X, Rosenkilde MM, Hwang ST, Volkman BF Proc Natl Acad Sci U S A. 2017 Nov 6. pii: 201704958. doi:, 10.1073/pnas.1704958114. PMID:29109267 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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