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The structural basis for intramembrane assembly of an activating immunoreceptor complex
Matthew E Call1, Kai W Wucherpfennig, James J Chou
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
Nature Immunology
|October 5, 2010
Summary
Researchers uncovered the structure of immune cell-activating receptors, revealing how protein subunits assemble via transmembrane domains. This electrostatic network is crucial for forming functional immune receptor complexes.
Area of Science:
- Immunology
- Structural Biology
- Molecular Biology
Background:
- Immune cell activation relies on multisubunit receptors with distinct ligand recognition and signaling functions.
- These receptors assemble through interactions within their transmembrane domains, often involving charged residues.
Purpose of the Study:
- To determine the NMR structure of the assembled natural killer (NK) cell-activating receptor NKG2C complexed with the DAP12 signaling module.
- To investigate the role of intramembrane polar motifs in the assembly of various activating immunoreceptors.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to elucidate the structure of the NKG2C-DAP12 complex.
- Functional mutagenesis to assess the importance of specific residues and motifs in receptor assembly.
Main Results:
- The NMR structure revealed a heterotrimeric assembly of NKG2C and DAP12, stabilized by an electrostatic network of five hydrophilic transmembrane residues.
- Mutagenesis studies confirmed that similar polar intramembrane motifs are essential for the assembly of other activating receptor complexes, including NKG2D-DAP10 and the T cell receptor (TCR)-CD3 complex.
Conclusions:
- A conserved polar intramembrane structural motif is critical for the assembly of diverse activating immunoreceptors.
- This finding provides fundamental insights into the molecular organization and function of immune cell surface receptors.
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