Structural basis for inhibition of a response regulator of σ S stability by a ClpXP antiadaptor

• Published in: Genes & development Vol. 33; no. 11-12; pp. 718 - 732
• Main Authors: Dorich, Victoria, Brugger, Christiane, Tripathi, Arti, Hoskins, Joel R, Tong, Song, Suhanovsky, Margaret M, Sastry, Amita, Wickner, Sue, Gottesman, Susan, Deaconescu, Alexandra M
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.06.2019
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Crystallography, X-Ray; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Escherichia coli Proteins - antagonists & inhibitors; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Models, Molecular; Protein Conformation; Protein Conformation, alpha-Helical; Protein Domains; Protein Stability; Research Paper; Sigma Factor - chemistry; Sigma Factor - metabolism; Transcription Factors - antagonists & inhibitors; Transcription Factors - chemistry; Transcription Factors - metabolism; crystallography; antiadaptor; stress response; bacteria; biochemistry; adaptor; ClpXP
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.320168.118

The stationary phase promoter specificity subunit σ (RpoS) is delivered to the ClpXP machinery for degradation dependent on the adaptor RssB. This adaptor-specific degradation of σ provides a major point for regulation and transcriptional reprogramming during the general stress response. RssB is an atypical response regulator and the only known ClpXP adaptor that is inhibited by multiple but dissimilar antiadaptors (IraD, IraP, and IraM). These are induced by distinct stress signals and bind to RssB in poorly understood manners to achieve stress-specific inhibition of σ turnover. Here we present the first crystal structure of RssB bound to an antiadaptor, the DNA damage-inducible IraD. The structure reveals that RssB adopts a compact closed architecture with extensive interactions between its N-terminal and C-terminal domains. The structural data, together with mechanistic studies, suggest that RssB plasticity, conferred by an interdomain glutamate-rich flexible linker, is critical for regulation of σ degradation. Structural modulation of interdomain linkers may thus constitute a general strategy for tuning response regulators.