Stability of 20S Proteasome Configurations: Preopening the Axial Gate
Mass spectrometry studies of the stability of the S. cerevisiae 20S proteasome from 11 to 55 °C reveal a series of related configurations and coupled transitions that appear to be associated with opening of the proteolytic core. We find no evidence for dissociation, and all transitions are reversibl...
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Veröffentlicht in: | The journal of physical chemistry letters 2023-06, Vol.14 (21), p.5014-5017 |
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creator | Henderson, Lucas W. Sharon, Edie M. Gautam, Amit K. S. Anthony, Adam J. Jarrold, Martin F. Russell, David H. Matouschek, Andreas Clemmer, David E. |
description | Mass spectrometry studies of the stability of the S. cerevisiae 20S proteasome from 11 to 55 °C reveal a series of related configurations and coupled transitions that appear to be associated with opening of the proteolytic core. We find no evidence for dissociation, and all transitions are reversible. A thermodynamic analysis indicates that configurations fall into three general types of structures: enthalpically stabilized, tightly closed (observed as the +54 to +58 charge states) configurations; high-entropy (+60 to +66) states that are proposed as precursors to pore opening; and larger (+70 to +79) partially and fully open pore structures. In the absence of the 19S regulatory unit, the mechanism for opening the 20S pore appears to involve a charge-priming process that loosens the closed-pore configuration. Only a small fraction (≤2%) of these 20S precursor configurations appear to open and thus expose the catalytic cavity. |
doi_str_mv | 10.1021/acs.jpclett.3c01040 |
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In the absence of the 19S regulatory unit, the mechanism for opening the 20S pore appears to involve a charge-priming process that loosens the closed-pore configuration. 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subjects | Physical Insights into Chemistry, Catalysis, and Interfaces Proteasome Endopeptidase Complex - chemistry Proteasome Endopeptidase Complex - metabolism Proteolysis Saccharomyces cerevisiae - metabolism |
title | Stability of 20S Proteasome Configurations: Preopening the Axial Gate |
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