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
Hauptverfasser: Henderson, Lucas W., Sharon, Edie M., Gautam, Amit K. S., Anthony, Adam J., Jarrold, Martin F., Russell, David H., Matouschek, Andreas, Clemmer, David E.
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container_end_page 5017
container_issue 21
container_start_page 5014
container_title The journal of physical chemistry letters
container_volume 14
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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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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