HLA-DM Stabilizes the Empty MHCII Binding Groove: A Model Using Customized Natural Move Monte Carlo.
Demharter S., Knapp B., Deane C., Minary P.
MHC class II molecules bind peptides derived from extracellular proteins that have been ingested by antigen-presenting cells and display them to the immune system. Peptide loading occurs within the antigen-presenting cell and is facilitated by HLA-DM. HLA-DM stabilizes the open conformation of the MHCII binding groove when no peptide is bound. While a structure of the MHCII/HLA-DM complex exists, the mechanism of stabilization is still largely unknown. Here, we applied customized Natural Move Monte Carlo to investigate this interaction. We found a possible long-range mechanism that implicates the configuration of the membrane-proximal globular domains in stabilizing the open state of the empty MHCII binding groove.