A structure for the trimeric MHC class II-associated invariant chain transmembrane domain

Area of Science:

• Immunology and Structural Biology

Background:

• The invariant chain (Ii) is crucial for Major Histocompatibility Complex (MHC) assembly and antigen presentation.
• Ii's transmembrane domain is essential for its function in the immune system and forms trimers.

Purpose of the Study:

• To determine the structure of the invariant chain's transmembrane domain.
• To provide a structural model of the transmembrane domain using experimental and computational methods.

Main Methods:

• Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy.
• Site-specific infrared dichroism and molecular dynamics (MD) simulations.
• Isotopic labeling ((13)C=(18)O) at ten different residues.

Main Results:

• The transmembrane domain adopts an alpha-helical structure.
• A structural model revealed a left-handed coiled coil with an average helix tilt of 13 degrees.
• Specific residues (Gln47, Thr50) play key roles in trimer formation and interhelical interactions.

Conclusions:

• The study resolves the backbone structure of the invariant chain's transmembrane domain.
• The determined structure provides insights into the molecular mechanisms of MHC assembly and immune function.