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Full-Text Articles in Molecular Biology
Quaternary Dynamics And Plasticity Underlie Small Heat Shock Protein Chaperone Function, Florian Stengel, Andrew J. Baldwin, Alexander J. Painter, Nomalie Jaya, Eman Basha, Lewis E. Kay, Elizabeth Vierling, Carol V. Robinson, Justin L. P. Benesch
Quaternary Dynamics And Plasticity Underlie Small Heat Shock Protein Chaperone Function, Florian Stengel, Andrew J. Baldwin, Alexander J. Painter, Nomalie Jaya, Eman Basha, Lewis E. Kay, Elizabeth Vierling, Carol V. Robinson, Justin L. P. Benesch
Elizabeth Vierling
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 …
Substrate Binding Site Flexibility Of The Small Heat Shock Protein Molecular Chaperones, Nomalie Jaya, Victor Garcia, Elizabeth Vierling
Substrate Binding Site Flexibility Of The Small Heat Shock Protein Molecular Chaperones, Nomalie Jaya, Victor Garcia, Elizabeth Vierling
Elizabeth Vierling
Small heat shock proteins (sHSPs) serve as a first line of defense against stress-induced cell damage by binding and maintaining denaturing proteins in a folding-competent state. In contrast to the well-defined substrate binding regions of ATP-dependent chaperones, interactions between sHSPs and substrates are poorly understood. Defining substrate-binding sites of sHSPs is key to understanding their cellular functions and to harnessing their aggregation-prevention properties for controlling damage due to stress and disease. We incorporated a photoactivatable cross-linker at 32 positions throughout a well-characterized sHSP, dodecameric PsHsp18.1 from pea, and identified direct interaction sites between sHSPs and substrates. Model substrates firefly luciferase …