Cells that are contaminated by a virus or bring a carcinogenic anomaly, for example, produce proteins foreign to the body. Antigenic peptides resulting from the degradation of these exogenous proteins inside the cell are loaded by the peptide-loading complex onto so-called significant histocompatibility complex particles (MHC for brief) and provided on the cell surface. There, they are specifically recognized by T-killer cells, which ultimately causes the removal of the infected cells. This is how our body immune system safeguards us versus pathogens.
Machine operates with atomic precision
The peptide-loading complex ensures that the MHC particles are properly filled with antigens. “The peptide-loading complex is a biological nanomachine that has to deal with atomic precision in order to effectively protect us versus pathogens that cause illness,” states Teacher Lars Schäfer, Head of the Molecular Simulation research group at the Centre for Theoretical Chemistry at RUB.
In previous studies, other teams successfully figured out the structure of the peptide-loading complex utilizing cryo-electron microscopy, however only with a resolution of about 0.6 to 1.0 nanometres, i.e. not in atomic detail. Based upon these speculative data, Schäfer’s research study group in collaboration with Professor Gunnar Schröder from Forschungszentrum Jülich has actually now succeeded in producing an atomic structure of the peptide-loading complex.
Exploring structure and characteristics
The atomic design made it possible for the scientists to perform detailed molecular characteristics computer simulations of the peptide-loading complex and thus to study not only the structure but likewise the characteristics of the biological nanomachine.
Because the simulated system is incredibly big with its 1.6 million atoms, the computing time at the Leibnitz Supercomputing Centre in Munich helped this job substantially.
Direct intervention in immune processes
The atomic design of the peptide-loading complex now helps with more studies. For example, some infections attempt to cheat our immune system by selectively switching off certain elements of the peptide-loading complex. “One feasible objective we ‘d like to pursue is the targeted intervention in these procedures,” concludes Schäfer.