Molecular architecture of mouse activating NKR-P1 receptors

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• The NKR-P1 family and Clr ligands mediate "missing self" recognition, vital for anti-tumor and anti-viral immunity.
• This system also plays roles in eliminating stressed cells, T cell responses, and hypertension.

Purpose of the Study:

• To determine the three-dimensional structure of the extracellular domain of the mouse NK cell receptor mNKR-P1Aex.
• To elucidate the structural basis for receptor-ligand interactions within the NKR-P1 family.

Main Methods:

• X-ray diffraction was used to determine the 3D structure of mNKR-P1Aex.
• Comparative analysis with other C-type lectin-like domain (CTLD) receptors.

Main Results:

• The structure reveals a core CTLD with an extended loop involved in domain swapping and dimerization.
• This domain swapping creates a compact interaction interface.
• A second dimerization interface is similar to other CTLD NK receptors.

Conclusions:

• The determined structure of mNKR-P1Aex provides insights into its function in "missing self" recognition.
• An evolutionarily conserved loop is proposed to be critical for ligand binding.
• The findings support a functional dimeric form of the receptor involved in immune surveillance.