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Proposing Institution

Theoretical Chemistry, Ruhr-University Bochum
Project Manager

Prof. Lars Schäfer
Universitaetsstr. 150
44801 Bochum
Major histocompatibility complex class I molecules (MHCI) are a crucial component of the immune system, as they signal when a cell has been compromised by a viral infection or cancer-causing mutation. To do so, MHCI expose antigen peptides at the cell surface. For proper function, each MHCI needs a peptide to bind (“be loaded”) in its binding groove. This process is controlled by the peptide-loading complex (PLC), a multi-protein assembly anchored to the endoplasmic reticulum membrane. The PLC contains no less than eight protein chains. While the structure of most of these components has been resolved, little is known about the global organisation of the complex.Using molecular dynamics (MD) simulations, we propose to study the structure and dynamics of the PLC. In previous works, we have characterised the interactions stabilising the functional components of the complex. For the first time, it is now possible to study the full PLC ‘in silico’. This, however, is a formidable task and a computationally very demanding endeavour, which requires the HPC resources available at LRZ. We have developed a robust strategy whereby we can build the complete PLC in a series of incremental steps, starting from a mimimal, functional sub-complex.In addition to novel, fundamental knowledge of adaptive immunity at the molecular level, we expect that our results will foster new biochemical and structural studies, as we propose testable hypotheses relating to PLC organisation.

Impressum, Conny Wendler