Project description
The mechanism of interaction of intrinsically disordered proteins
Unlike most proteins, intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structures under physiological conditions in vitro. Yet they carry out an important array of biological functions. The EU-funded MultiMotif project is interested to understand the molecular mechanisms of IDP interactions. Scientists will focus on endocytosis, the process by which cells take up material including nutrients and fluids from the surrounding environment. Endocytosis involves the engulfment of molecules into vesicles in an energy-dependent process that involves various proteins such as clathrin as well as IDPs. The work will provide key evidence of how the linear motifs of IDPs mediate interaction with other proteins and lipids.
Objective
Linear motifs are short sequence stretches that occur in intrinsically disordered protein regions (IDRs) lacking stable secondary and tertiary structure, and mediate vital interactions within various biological systems. An exemplary system for the presence of IDRs and a high concentration of linear motifs is the clathrin mediated endocytosis machinery of the eukaryotic cell, where a complex interaction network of IDR-rich adaptor proteins enables both protein and lipid interactions. The molecular mechanism of such interactions, especially when multiple motifs act in concert, is however only poorly understood particularly since the dynamic and flexible nature of IDRs makes them a very difficult object to study. I aim to develop an integrative approach based on single molecule fluorescence and NMR spectroscopies to characterize the molecular principles of IDRs in clathrin mediated endocytosis. A systematic analysis of IDRs with different types of motifs and various interaction partners will not only shed light on the molecular functions of linear motifs within endocytosis, but also on how multiplicities of linear motifs may work in various biological processes in general. In vitro structural studies will be connected with single molecule imaging to relate molecular conformation with function within the cell.
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Funding Scheme
ERC-STG - Starting GrantHost institution
12489 Berlin
Germany