Background: A novel chaperone, cpSRP43, recognizes and disassembles the aggregates formed by its client proteins.
Results: The client proteins of cpSRP43 form stable disc-shaped aggregates with the chaperone recognition motif displayed onthe surface.
Conclusion: The surface-exposed motif on the aggregate allows it to be recognized by its chaperone.
Significance: Understanding the structure and energetics of protein aggregates provides insights into the mechanism of theirDISASSEMBLY.Protein aggregation is detrimental to the maintenance of proper protein homeostasis in all cells. To overcome this problem, cells have evolved a network of molecular chaperones to prevent protein aggregation and even reverse existing protein aggregates. The most extensively studied disaggregase systems are ATP-driven macromolecular machines. Recently, we reported an alternative disaggregase system in which the 38-kDa subunit of chloroplast signal recognition particle (cpSRP43) efficiently reverses the aggregation of its substrates, the light-harvesting chlorophyll a/b-binding (LHC) proteins, in the absence of external energy input. To understand the molecular mechanism of this novel activity, here we used biophysical and biochemical methods to characterize the structure and nature of LHC protein aggregates. We show that LHC proteins form micellar, disc-shaped aggregates that are kinetically stable and detergent-resistant. Despite the nonamyloidal nature, the LHC aggregates have a defined global organization, displaying the chaperone recognition motif on its solvent-accessible surface. These findings suggest an attractive mechanism for recognition of the LHC aggregate by cpSRP43 and provide important constraints to define the capability of this chaperone.
Keywords: Aggregation; Enzyme Mechanisms; Light-harvesting Complex; Membrane Biophysics; Membrane Protein Biogenesis; Molecular Chaperone; Protein Aggregation; Signal Recognition Particle.