Dissecting Heterogeneous Molecular Chaperone Complexes Using a Mass Spectrum Deconvolution Approach

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• 作者：Florian Stengel<sup>1sup><sup> ; sup><sup>6sup><sup> ; sup><sup>8sup> ; Andrew  ; J. Baldwin<sup>2sup><sup> ; sup><sup>8sup> ; Matthew  ; F. Bush<sup>1sup><sup> ; sup><sup>7sup> ; Gillian  ; R. Hilton<sup>1sup> ; Hadi Lioe<sup>1sup> ; Eman Basha<sup>3sup><sup> ; sup><sup>4sup> ; Nomalie Jaya<sup>4sup> ; Elizabeth Vierling<sup>5sup> ; Justin  ; L.P. Benesch<sup>1sup><sup> ; sup><sup>justin.benesch@chem.ox.ac.uksup>
• 刊名：Chemistry & Biology
• 出版年：2012
• 期刊代码：20_10745521
• 类别：ch
• 出版时间：25 May, 2012
• 卷：19
• 期：5
• 页码：599-607
• 文件大小：1065 K

摘要

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ss="h3">Summary

Small heat-shock proteins (sHSPs) are molecular chaperones that prevent irreversible aggregation through binding nonnative target proteins. Due to their heterogeneity, these sHSP:target complexes remain poorly understood. We present a nanoelectrospray mass spectrometry analysis algorithm for聽estimating the distribution of stoichiometries comprising a polydisperse ensemble of oligomers. We thus elucidate the organization of complexes formed between sHSPs and different target proteins. We find that binding is mass dependent, with the resultant complexes reflecting the native quaternary architecture of the target, indicating that protection happens early in the denaturation. Our data therefore explain the apparent paradox of how variable complex morphologies result from the generic mechanism of protection afforded by sHSPs. Our approach is applicable to a range of polydisperse proteins and provides a means for the automated and accurate interpretation of mass spectra derived from heterogeneous protein assemblies.