Quaternary dynamics and plasticity underlie small heat shock protein chaperone function.
Proc Natl Acad Sci U S A
; 107(5): 2007-12, 2010 Feb 02.
Article
em En
| MEDLINE
| ID: mdl-20133845
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Choque Térmico Pequenas
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article