Structures of the multi-domain oxygen sensor DosP: remote control of a c-di-GMP phosphodiesterase by a regulatory PAS domain.

Autor: Wu W; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Kumar P; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Brautigam CA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Tso SC; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Baniasadi HR; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Kober DL; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. daniel.kober@utsouthwestern.edu., Gilles-Gonzalez MA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. marie-alda.gilles-gonzalez@utsouthwestern.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 07; Vol. 15 (1), pp. 9653. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1038/s41467-024-53942-7
Abstrakt: 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 determine 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 containing domain 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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