In collaboration with researchers at Martin Luther University Halle-Wittenberg, Biochemists at Goethe University Frankfurt and the Max Planck Institute of Biophysics have uncovered the inner workings of a complex molecular machine in cells. The MHC-1 complex pre-selects and transmits information to the immune system in order to fight viruses, bacteria, parasites, and cancers.
The immune system helps fight against unwelcome invaders, but to initiate this process information should be pre-selected and transmitted to the immune system. This occurs in the form of small protein fragments presented on the cell surface using a highly complex molecular machine the MHC-1 molecule.
While cancerous or infected cells are quickly identified and eliminated, viruses and tumors can also trick the immune system thus escaping immune surveillance. Ambiguous messages can also lead to autoimmune diseases or chronic inflammation.
The highly complex molecular machine in the cell's interior selects the relevant protein fragments. It also coordinates the loading of MHC-I molecules, which is a particularly important process. Researchers published their finding on the molecular architecture and inner workings of the MHC-I peptide-loading complex in the journal Nature.
Dr. Simon Trowitzsch explained, "We had to pull out all the stops to prepare this extremely fragile complex for structural analyses." The researchers developed a viral molecular bait. This allowed them to isolate the native MHC-I peptide-loading complex from the endoplasmic reticulum.
Researchers were able to look closely at the MHC-I peptide-loading complex and to determine its molecular structure by using cryo-electron microscopy. MHC-I peptide-loading complex is about a hundred thousand times smaller than a pinhead, and cryo-electron microscopy allowed them to observe this structure.
Researchers identified how information was generated from the cell to the immune system. Cell structure showed how transport proteins in the membrane, folding enzymes, and MHC-I molecule worked together as a highly dynamic complex.
The research identified how the information transported by MHC-I peptide loading complex filters out only required fragments which the immune system's effector cells needed. The antigen selection process could be elucidated with greater precision and this knowledge can further guide immunotherapies.