Heme pocket modulates protein conformation and diguanylate cyclase activity of a tetrameric globin coupled sensor.

Autor: Potter JR; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA., Rivera S; Department of Chemistry, Emory University, Atlanta, GA 30322, USA., Young PG; Department of Chemistry, Emory University, Atlanta, GA 30322, USA., Patterson DC; Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA., Namitz KE; Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA; The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA., Yennawar N; The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA., Kincaid JR; Department of Chemistry, Marquette University, Milwaukee, WI 53233, USA. Electronic address: james.kincaid@marquette.edu., Liu Y; Department of Chemistry, Marquette University, Milwaukee, WI 53233, USA; Department of Chemistry, University of Akron, Akron, OH 44325, USA. Electronic address: yliu1@uakron.edu., Weinert EE; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA; Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA. Electronic address: emily.weinert@psu.edu.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2024 Sep; Vol. 258, pp. 112638. Date of Electronic Publication: 2024 Jun 08.
DOI: 10.1016/j.jinorgbio.2024.112638
Abstrakt: Bacteria use the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) to control biofilm formation and other key phenotypes in response to environmental signals. Changes in oxygen levels can alter c-di-GMP signaling through a family of proteins termed globin coupled sensors (GCS) that contain diguanylate cyclase domains. Previous studies have found that GCS diguanylate cyclase activity is controlled by ligand binding to the heme within the globin domain, with oxygen binding resulting in the greatest increase in catalytic activity. Herein, we present evidence that heme-edge residues control O 2 -dependent signaling in PccGCS, a GCS protein from Pectobacterium carotovorum, by modulating heme distortion. Using enzyme kinetics, resonance Raman spectroscopy, small angle X-ray scattering, and multi-wavelength analytical ultracentrifugation, we have developed an integrated model of the full-length PccGCS tetramer and have identified conformational changes associated with ligand binding, heme conformation, and cyclase activity. Taken together, these studies provide new insights into the mechanism by which O 2 binding modulates activity of diguanylate cyclase-containing GCS proteins.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Emily Weinert reports financial support was provided by National Science Foundation. Emily Weinert reports financial support was provided by Herman Frasch Foundation for Chemical Research. Yilin Liu reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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