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Published May 10, 2013 | Supplemental Material + Published
Journal Article Open

Mechanism of an ATP-independent Protein Disaggregase - I. Structure of a Membrane Protein Aggregate Reveals a Mechanism of Recognition by its Chaperone


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.

Additional Information

© 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, February 18, 2013, and in revised form, March 13, 2013 Published, JBC Papers in Press, March 22, 2013. Supported by a grant from the Betty and Gordon Moore Foundation. Supported by the David and Lucile Packard Fellowship in science and engineering, the Henry Dreyfus Teacher-Scholar Award, and the Breakthroughs in Gerontology award from the American Federation for Aging Research. We thank A. N. Murray and Dr. J. W. Kelly for recrystallized ThT and fibrilized Aβ_(1–40), A. McDowall for EM analyses, members of the Proteome Exploration Laboratory for mass spectrometry assistance, and members of the Shan group for helpful comments on the manuscript. The Proteome Exploration Laboratory is supported by the Betty and Gordon Moore Foundation and the Beckman Institute. AFM studies were supported by United States Department of Energy Grant DE-FG03-01ER46175 (to J. Heath).

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Published - J._Biol._Chem.-2013-Nguyen-13420-30.pdf

Supplemental Material - jbc.M113.462812-1.docx


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