The compartmentalization of eukaryotic cells into organelles is central to their ability to differentiate and perform complex functions. A key part of this strategy is the ability to control ionic and molecular transport across the lipid membranes delineating these subcellular structures and the cell itself. A managed information flow across membranes is critical for intra- and inter-cellular communication. Loss of control over the transmembrane processes is often associated with disease and infection.
Characterizing the function of the large and complex protein assemblies involved in membrane transport and cellular communication is a central goal of the CRC 807. This effort ranges from determining the composition of the assemblies and the process of their formation from multiple peptide chains and co-factors, over characterizing their structure and function at both molecular and cellular scales, to examining the elaborate mechanisms that establish lipid and protein homeostasis.
Membrane complexes facilitate the translocation of proteins, antigens, xenobiotics, or information reporting on inflammation and ER stress. Examples studied include (A) the translocase of the outer chloroplast membrane, (B) the MHC I peptide loading complex required for adaptive immunity, (C) the transmembrane receptor Ire1 that monitors aberrant lipid compositions and triggers the unfolded protein response, and (D) the tripartite multidrug export complexes AcrB connecting inner and outer bacterial membranes. E) Mass spectrometry opens a window into the hierarchical assembly process, stoichiometric composition, and intermediate binding states. F) Functional conformational dynamics and assembly of membrane complexes can be monitored by single-molecule based fluorescence techniques.