<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor"^^ . "The activation status of natural killer (NK) cells is determined by the integration of activating and inhibitory signals at the immunological synapse between the NK cell and a target cell. In this work we studied the activating and inhibitory signals of NK cells: The presence of cholesterol-rich membrane domains at the activating immunological synapse and the absence of these membrane domains at inhibitory immunological synapses has supported the role of lipid rafts in the regulation of NK cell activation. Several activating NK cell receptors are known to localize into these lipid rafts upon ligation and thereby influence the functional outcome of a NK cell-target cell contact. How these receptors are recruited into these important membrane domains remains unknown though. In order to elucidate the molecular basis of these mechanisms we studied the structural requirements of the human activating NK cell receptors 2B4 and NKG2D for receptor recruitment into detergent-resistant membrane (DRM) fractions as a model for lipid raft association. Structural requirements in 2B4 for DRM recruitment could be identified at the luminal side of the transmembrane domain and in the CxC motif near the cytoplasmic side of the transmembrane domain. Similar to 2B4, we could determine a requirement for the NKG2D transmembrane domain for DRM recruitment. However, DRM recruitment of both receptors was independent from signal transduction. Thus our study presents data about potential molecular mechanisms involved in lipid raft recruitment. In order to study NK cell inhibition, we developed inhibitors against the sialic acidbinding receptor Siglec-7 on NK cells. This receptor is known to exert inhibitory effects on the function of NK cells and is harnessed by certain pathogens and malignancies for immune evasion. The inhibitors were designed by collaborating biochemists based on the structure of unmodified sialic acid. We screened a broad collection of inhibitors and tested these in functional assays for their capacity to block Siglec-7 receptor-ligand interaction and their effect on NK cell activity. In conclusion, this collaborative study was able to generate the first inhibitor with high affinity against Siglec-7 and with a functional effect on the cytotoxicity of NK cells."^^ . "2012" . . . . . . . . "Stephan Alexander"^^ . "Gütgemann"^^ . "Stephan Alexander Gütgemann"^^ . . . . . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor (PDF)"^^ . . . "Dissertation_StephanG_final.pdf"^^ . . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Molecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #13499 \n\nMolecular basis for the lipid raft recruitment of NK cell receptors and development of a sialic acid-based Siglec-7 inhibitor\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .