McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation
In Gram-positive bacteria, the McsB protein arginine kinase is central to protein quality control, labeling aberrant molecules for degradation by the ClpCP protease. Despite its importance for stress response and pathogenicity, it is still elusive how the bacterial degradation labeling is regulated....
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications
2021
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| _version_ | 1797090933281390592 |
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| author | Hajdusits, B Suskiewicz, MJ Hundt, N Meinhart, A Kurzbauer, R Leodolter, J Kukura, P Clausen, T |
| author_facet | Hajdusits, B Suskiewicz, MJ Hundt, N Meinhart, A Kurzbauer, R Leodolter, J Kukura, P Clausen, T |
| author_sort | Hajdusits, B |
| collection | OXFORD |
| description | In Gram-positive bacteria, the McsB protein arginine kinase is central to protein quality control, labeling aberrant molecules for degradation by the ClpCP protease. Despite its importance for stress response and pathogenicity, it is still elusive how the bacterial degradation labeling is regulated. Here, we delineate the mechanism how McsB targets aberrant proteins during stress conditions. Structural data reveal a self-compartmentalized kinase, in which the active sites are sequestered in a molecular cage. The ‘closed’ octamer interconverts with other oligomers in a phosphorylation-dependent manner and, unlike these ‘open’ forms, preferentially labels unfolded proteins. In vivo data show that heat-shock triggers accumulation of higher order oligomers, of which the octameric McsB is essential for surviving stress situations. The interconversion of open and closed oligomers represents a distinct regulatory mechanism of a degradation labeler, allowing the McsB kinase to adapt its potentially dangerous enzyme function to the needs of the bacterial cell. |
| first_indexed | 2024-03-07T03:25:46Z |
| format | Journal article |
| id | oxford-uuid:b8f9df60-57e9-4a76-8251-f102067ebbef |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:25:46Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:b8f9df60-57e9-4a76-8251-f102067ebbef2022-03-27T04:59:49ZMcsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b8f9df60-57e9-4a76-8251-f102067ebbefEnglishSymplectic ElementseLife Sciences Publications2021Hajdusits, BSuskiewicz, MJHundt, NMeinhart, AKurzbauer, RLeodolter, JKukura, PClausen, TIn Gram-positive bacteria, the McsB protein arginine kinase is central to protein quality control, labeling aberrant molecules for degradation by the ClpCP protease. Despite its importance for stress response and pathogenicity, it is still elusive how the bacterial degradation labeling is regulated. Here, we delineate the mechanism how McsB targets aberrant proteins during stress conditions. Structural data reveal a self-compartmentalized kinase, in which the active sites are sequestered in a molecular cage. The ‘closed’ octamer interconverts with other oligomers in a phosphorylation-dependent manner and, unlike these ‘open’ forms, preferentially labels unfolded proteins. In vivo data show that heat-shock triggers accumulation of higher order oligomers, of which the octameric McsB is essential for surviving stress situations. The interconversion of open and closed oligomers represents a distinct regulatory mechanism of a degradation labeler, allowing the McsB kinase to adapt its potentially dangerous enzyme function to the needs of the bacterial cell. |
| spellingShingle | Hajdusits, B Suskiewicz, MJ Hundt, N Meinhart, A Kurzbauer, R Leodolter, J Kukura, P Clausen, T McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
| title | McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
| title_full | McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
| title_fullStr | McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
| title_full_unstemmed | McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
| title_short | McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
| title_sort | mcsb forms a gated kinase chamber to mark aberrant bacterial proteins for degradation |
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