Structural basis of DAP12-associated intramembrane immunoreceptor assembly. (138.16)
| Autor: | Matthew Call, Kai Wucherpfennig, James Chou |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:138.16-138.16 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.184.supp.138.16 |
| Popis: | Many of the molecular sensors that alert lymphocytes to dangerous events such as infection or transformation are modular receptors constructed from ligand-binding subunits and signaling subunits that assemble through specific contacts within the lipid bilayer to form functional complexes. Structure-function studies focusing on the extracellular and cytoplasmic domains of activating immunoreceptors like the T cell receptor (TCR)-CD3 complex have yielded a vast store of knowledge on the mechanisms governing ligand binding and the resulting intracellular biochemical cascades. However, the mechanisms physically linking these events across the membrane to initiate immune activation remain poorly defined, and structural information on the membrane-embedded portions of receptor complexes will be critical for developing more precise models. We previously published the first structure of an immunoreceptor-associated transmembrane (TM) signaling module, the TCR-associated ζζTM dimer. We now present the NMR structure of DAP12, a functional homologue of ζζ that provides the ITAM-based signaling capabilities to more than a dozen activating receptors expressed by NK cells and other hematopoietic lineages. We have also solved a structure of the trimolecular complex DAP12-TM forms with the NK cell receptor NKG2C. These structures reveal features that allow DAP12 to assemble with a multitude of different receptors with disparate TM sequences through focused polar contacts within the membrane. |
| Databáze: | OpenAIRE |
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