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Small Heat Shock Proteins (sHSPs) are a diverse family of molecular chaperones that prevent protein aggregation by binding clients destabilized during cellular stress. Here we probe the architecture and dynamics of complexes formed between an oligomeric sHSP and client by employing unique mass spectrometry strategies. We observe over 300 different stoichiometries of interaction, demonstrating that an ensemble of structures underlies the protection these chaperones confer to unfolding clients. This astonishing heterogeneity not only makes the system quite distinct in behavior to ATP-dependent chaperones, but also renders it intractable by conventional structural biology approaches. We find that thermally regulated quaternary dynamics of the sHSP establish and maintain the plasticity of the system. This extends the paradigm that intrinsic dynamics are crucial to protein function to include equilibrium fluctuations in quaternary structure, and suggests they are integral to the sHSPs' role in the cellular protein homeostasis network.

Original publication

DOI

10.1073/pnas.0910126107

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

02/02/2010

Volume

107

Pages

2007 - 2012

Keywords

Biophysical Phenomena, Heat-Shock Proteins, Heat-Shock Proteins, Small, Luciferases, Firefly, Models, Molecular, Molecular Chaperones, Multiprotein Complexes, Peas, Plant Proteins, Protein Multimerization, Protein Structure, Quaternary, Recombinant Proteins, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Thermodynamics