CDB15:0000206 CCL17 — CCR8
Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Sheep
Title
Journal:; Year Published:
Abstract
Structures of thymus and activation-regulated chemokine (TARC).
Acta crystallographica. Section D, Biological crystallography, 2003; PubMed, Homo sapiens CCL17 — Homo sapiens CCR8
ABSTRACT: Thymus and activation-regulated chemokine (TARC) is a CC chemokine that is mainly expressed in the thymus. TARC interacts primarily with the CCR4 receptor and to a lesser extent with the CCR8 receptor. The structures of TARC have been solved by molecular replacement in two space groups, triclinic (P1) and tetragonal (P4(1)), and refined to resolutions of 1.72 and 2.1 A, respectively, with R factors of 19.8% (R(free) = 24.1%) and 19.8% (R(free) = 27.7%), respectively. The search model originated from the crystal structure of another chemokine, RANTES, and proved to be only modestly similar to the refined structure of TARC. Whereas the tetragonal structure was easily solved using the program AMoRe, solution of the triclinic structure proved to be quite challenging and was obtained by combining the results from four different molecular-replacement programs (AMoRe, CNS, BEAST and EPMR), with subsequent extension of the gathered information. The tertiary structure of TARC is similar to that of other CC chemokines, with a three-stranded antiparallel beta-sheet flanked by a C-terminal helix. Both quaternary structures consist of dimers, which in the triclinic crystals pack further into tetramers. The TARC dimers are similar to those observed previously in the crystal structures of both MCP-1 and RANTES.
Identification of the CC chemokines TARC and macrophage inflammatory protein-1 beta as novel functional ligands for the CCR8 receptor.
European journal of immunology, 1998; PubMed, Homo sapiens CCL17 — Homo sapiens CCR8
ABSTRACT: Chemokines are key molecules in directing leukocyte migration toward sites of inflammation. We have previously cloned a putative CC chemokine receptor gene, TER1, whose expression is restricted to lymphoid tissues and cell lines. Recently, this receptor has been shown to signal in response to the human CC chemokine I-309 and thus it has been renamed CCR8 according to the current nomenclature. In the present study, we report the identification of the CC chemokines thymus and activation-regulated cytokine (TARC) and macrophage inflammatory protein-1 beta (MIP-1 beta) as CCR8 ligands, as they induce chemotaxis in CCR8 Jurkat stable transfectants. Furthermore, we have generated a polyclonal antiserum that is able to recognize the CCR8 molecule in transfectant lysates. The pattern of CCR8 mRNA expression and the functional effects exerted by its ligand suggest that the triggering of this receptor may regulate multiple functions including activation, migration and proliferation of lymphoid cells.