Jacob R. Potter , Shannon Rivera , Paul G. Young , Dayna C. Patterson , Kevin E. Namitz , Neela Yennawar , James R. Kincaid , Yilin Liu , Emily E. Weinert
{"title":"血红素口袋调节蛋白质构象和四聚体球蛋白耦合传感器的二聚体环化酶活性","authors":"Jacob R. Potter , Shannon Rivera , Paul G. Young , Dayna C. Patterson , Kevin E. Namitz , Neela Yennawar , James R. Kincaid , Yilin Liu , Emily E. Weinert","doi":"10.1016/j.jinorgbio.2024.112638","DOIUrl":null,"url":null,"abstract":"<div><p>Bacteria use the second messenger cyclic dimeric guanosine monophosphate (<em>c</em>-di-GMP) to control biofilm formation and other key phenotypes in response to environmental signals. Changes in oxygen levels can alter <em>c</em>-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<sub>2</sub>-dependent signaling in <em>Pcc</em>GCS, a GCS protein from <em>Pectobacterium carotovorum</em>, 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 <em>Pcc</em>GCS 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<sub>2</sub> binding modulates activity of diguanylate cyclase-containing GCS proteins.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"258 ","pages":"Article 112638"},"PeriodicalIF":3.8000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heme pocket modulates protein conformation and diguanylate cyclase activity of a tetrameric globin coupled sensor\",\"authors\":\"Jacob R. Potter , Shannon Rivera , Paul G. Young , Dayna C. Patterson , Kevin E. Namitz , Neela Yennawar , James R. Kincaid , Yilin Liu , Emily E. Weinert\",\"doi\":\"10.1016/j.jinorgbio.2024.112638\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Bacteria use the second messenger cyclic dimeric guanosine monophosphate (<em>c</em>-di-GMP) to control biofilm formation and other key phenotypes in response to environmental signals. Changes in oxygen levels can alter <em>c</em>-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<sub>2</sub>-dependent signaling in <em>Pcc</em>GCS, a GCS protein from <em>Pectobacterium carotovorum</em>, 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 <em>Pcc</em>GCS 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<sub>2</sub> binding modulates activity of diguanylate cyclase-containing GCS proteins.</p></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":\"258 \",\"pages\":\"Article 112638\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-06-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013424001624\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013424001624","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Heme pocket modulates protein conformation and diguanylate cyclase activity of a tetrameric globin coupled sensor
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 O2-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 O2 binding modulates activity of diguanylate cyclase-containing GCS proteins.
期刊介绍:
The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.