Structures of the multi-domain oxygen sensor DosP: remote control of a c-di-GMP phosphodiesterase by a regulatory PAS domain
Year: 2024
Type: article
Abstract: The heme-based direct oxygen sensor DosP degrades c-di-GMP, a second messenger nearly unique to bacteria. In stationary phase Escherichia coli , DosP is the most abundant c-di-GMP phosphodiesterase. Ligation of O 2 to a heme-binding PAS domain (hPAS) of the protein enhances the phosphodiesterase through an allosteric mechanism that has remained elusive. We determined six structures of full-length DosP in its aerobic or anaerobic conformations, with or without c-di-GMP. DosP is an elongated dimer with the regulatory heme and phosphodiesterase separated by nearly 180 Å. In the absence of substrate, regardless of the heme status, DosP presents an equilibrium of two distinct conformations. Binding of substrate induces DosP to adopt a single, ON-state or OFF-state conformation depending on its heme status. Structural and biochemical studies of this multi-domain sensor and its mutants provide insights into signal regulation of second-messenger levels.
Source: Nature Communications
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Energy, U.S. Department of Health and Human Services, Oregon Health and Science University, University of Texas Southwestern Medical Center, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, Biological and Environmental Research
Awards: G1052650972, G1432493126, G2683375497, G2980993414, Structural and mechanistic basis for the maturation of site-one protease in the secretory pathway, The mechanistic basis for targeted protein degradation in lipid metabolism, Pacific Northwest Center for Cryo-EM, G6221506569, G8968209605, G9000060489
OpenAlex ID: W4404125645