Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• The Major Histocompatibility Complex (MHC) class I homolog, MICA, acts as a stress-inducible ligand.
• NKG2D is a C-type lectin-like activating immunoreceptor that binds to MICA.

Purpose of the Study:

• To determine the crystal structure of the MICA-NKG2D ligand-receptor complex.
• To elucidate the molecular interactions and structural basis of MICA binding to NKG2D.

Main Methods:

• X-ray crystallography was used to obtain the structure of the MICA-NKG2D complex.
• Structural analysis focused on the interfaces and conformational changes.

Main Results:

• The crystal structure shows an NKG2D homodimer bound to a MICA monomer.
• Binding interactions are extensive, complementary, and analogous to T cell receptor-MHC class I complexes.
• The alpha2-domain helix of MICA becomes ordered in the complex, and MICA's interdomain linker exhibits altered conformation.

Conclusions:

• The study provides detailed insights into the structural basis of MICA-NKG2D recognition.
• Understanding these interactions is crucial for comprehending immune responses to cellular stress.