Visualising chaperone-mediated processes

Visualising chaperone-mediated processes

Molecular chaperones are molecular motors that drive a variety of intracellular assembly and disassembly processes to catalyse protein folding, prevent aggregation and facilitate the recycling of the components of macromolecular complexes. These functions are vital to cellular homeostasis and chaperone malfunction underlies a range of neurodegenerative diseases and cancers. However, the molecular mechanisms of these processes and how they can be targeted pharmacologically are not well understood. Capitalising on our recent single-molecule imaging approach to visualise chaperone dynamics (Figure1; Nat Struct Mol Biol 2011, 18(3), 295-301) we now aim extend our mechanistic studies of role of Hsp70 family chaperones in its diverse cellular functions.

image - Molecular Machines

Figure 1: Fluorescence imaging approach to follow in real time the chaperone-mediated disassembly of the protein coat surrounding endocytic clathrin coated vesicles.Left: Selected snapshots from a time series (top) showing the fluorescence from clathrin and the chaperone Hsc70 in a coat visualised using the single-particle uncoating assay (shown schematically at the bottom). Right: The plot shows intensity traces of the clathrin (blue) and Hsc70 (orange) signals of a single coat during the uncoating reaction.