8t85 | pdb_00008t85
Structure of RssB bound to beryllofluoride
Structural highlights
FunctionRSSB_ECOLI Regulates the turnover of the sigma S factor (RpoS) by promoting its proteolysis in exponentially growing cells. Acts by binding and delivering RpoS to the ClpXP protease. RssB is not co-degraded with RpoS, but is released from the complex and can initiate a new cycle of RpoS recognition and degradation. In stationary phase, could also act as an anti-sigma factor and reduce the ability of RpoS to activate gene expression. Is also involved in the regulation of the mRNA polyadenylation pathway during stationary phase, probably by maintaining the association of PcnB with the degradosome.[HAMAP-Rule:MF_00958][1] [2] [3] [4] [5] [6] Publication Abstract from PubMedIn enterobacteria such as Escherichia coli, the general stress response is mediated by sigma(s), the stationary phase dissociable promoter specificity subunit of RNA polymerase. sigma(s) is degraded by ClpXP during active growth in a process dependent on the RssB adaptor, which is thought to be stimulated by the phosphorylation of a conserved aspartate in its N-terminal receiver domain. Here we present the crystal structure of full-length RssB bound to a beryllofluoride phosphomimic. Compared to the structure of RssB bound to the IraD anti-adaptor, our new RssB structure with bound beryllofluoride reveals conformational differences and coil-to-helix transitions in the C-terminal region of the RssB receiver domain and in the interdomain segmented helical linker. These are accompanied by masking of the alpha4-beta5-alpha5 (4-5-5) "signaling" face of the RssB receiver domain by its C-terminal domain. Critically, using hydrogen-deuterium exchange mass spectrometry, we identify sigma(s)-binding determinants on the 4-5-5 face, implying that this surface needs to be unmasked to effect an interdomain interface switch and enable full sigma(s) engagement and hand-off to ClpXP. In activated receiver domains, the 4-5-5 face is often the locus of intermolecular interactions, but its masking by intramolecular contacts upon phosphorylation is unusual, emphasizing that RssB is a response regulator that undergoes atypical regulation. Structure of phosphorylated-like RssB, the adaptor delivering sigma(s) to the ClpXP proteolytic machinery, reveals an interface switch for activation.,Brugger C, Schwartz J, Novick S, Tong S, Hoskins JR, Majdalani N, Kim R, Filipovski M, Wickner S, Gottesman S, Griffin PR, Deaconescu AM J Biol Chem. 2023 Dec;299(12):105440. doi: 10.1016/j.jbc.2023.105440. Epub 2023 , Nov 9. PMID:37949227[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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