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Expanded Coverage Of The 26s Proteasome Conformational Landscape Reveals Mechanisms Of Peptidase Gating

Title: Expanded Coverage Of The 26s Proteasome Conformational Landscape Reveals Mechanisms Of Peptidase Gating.
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Name(s): Eisele, Markus R., author
Reed, Randi G., author
Rudack, Till, author
Schweitzer, Andreas, author
Beck, Florian, author
Nagy, Istvan, author
Pfeifer, Guenter, author
Plitzko, Juergen M., author
Baumeister, Wolfgang, author
Tomko, Robert J., author
Sakata, Eri, author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2018-07-31
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The proteasome is the central protease for intracellular protein breakdown. Coordinated binding and hydrolysis of ATP by the six proteasomal ATPase subunits induces conformational changes that drive the unfolding and translocation of substrates into the proteolytic 20S core particle for degradation. Here, we combine genetic and biochemical approaches with cryo-electron microscopy and integrative modeling to dissect the relationship between individual nucleotide binding events and proteasome conformational dynamics. We demonstrate unique impacts of ATP binding by individual ATPases on the proteasome conformational distribution and report two conformational states of the proteasome suggestive of a rotary ATP hydrolysis mechanism. These structures, coupled with functional analyses, reveal key roles for the ATPases Rpt1 and Rpt6 in gating substrate entry into the core particle. This deepened knowledge of proteasome conformational dynamics reveals key elements of intersubunit communication within the proteasome and clarifies the regulation of substrate entry into the proteolytic chamber.
Identifier: FSU_libsubv1_wos_000440377500019 (IID), 10.1016/j.celrep.2018.07.004 (DOI)
Keywords: cryo-em structure, cryoelectron microscopy, molecular-dynamics, structural basis, 20s proteasomes, c-termini, core particle, eukaryotic proteasome, regulatory particle, substrate degradation
Publication Note: The publisher’s version of record is available at https://doi.org/10.1016/j.celrep.2018.07.004
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000440377500019
Owner Institution: FSU
Is Part Of: Cell Reports.
2211-1247
Issue: iss. 5, vol. 24

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Eisele, M. R., Reed, R. G., Rudack, T., Schweitzer, A., Beck, F., Nagy, I., … Sakata, E. (2018). Expanded Coverage Of The 26s Proteasome Conformational Landscape Reveals Mechanisms Of Peptidase Gating. Cell Reports. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000440377500019