Structural description of protein-protein interactions is the cornerstone of knowledge enabling detailed molecular understanding of processes such as receptor-ligand recognition within immune system, potentially leading to a design of targeted immunotherapeutics or drugs in general. Precise analysis of such interacting systems usually relies on X-ray structural analysis which is, however, dependent on successful preparation of diffracting crystals of the given protein complex – a task significantly more difficult for low-affinity or membrane protein complexes. On contrary, biophysical methods such as chemical cross-linking and hydrogen/deuterium exchange mass spectrometry or small-angle X-ray scattering enable to study protein interactions directly in solution.
Combination of these techniques will be used for detailed study and molecular description of interactions of an important human lymphocyte activating immunoreceptor CD69 with its newly described protein ligands – galectin 1, calprotectin, and S1P1R. Both galectin-1 and calprotectin also play role in immune response while S1P1R is a GPCR receptor and its interaction with the CD69 was mapped into transmembrane regions of both proteins, thus making it very challenging for structural studies. So far there is no detailed study describing these protein-protein complexes on molecular structural level, or their assembly within immune synapse on the membrane of a living cell.
This research project is currently supported by Czech Science Foundation grant 18-10687S
Deadline is closedChemistry: Structural and biophysical description of interactions of CD69, a human lymphocyte receptor, with its newly described protein ligands
