Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA
The complex metabolism of Escherichia coli has been extensively studied, including its response to oxygen availability. The ArcA/B two-component system (TCS) is the key regulator for the transition between these two environmental conditions and has been thoroughly characterized using genetic and bio...
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PeerJ Inc.
2023-10-01
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| author | Felipe Padilla-Vaca Javier de la Mora Rodolfo García-Contreras Jorge Humberto Ramírez-Prado Marcos Vicente-Gómez Francisco Vargas-Gasca Fernando Anaya-Velázquez Itzel Páramo-Pérez Ángeles Rangel-Serrano Patricia Cuéllar-Mata Naurú Idalia Vargas-Maya Bernardo Franco |
| author_facet | Felipe Padilla-Vaca Javier de la Mora Rodolfo García-Contreras Jorge Humberto Ramírez-Prado Marcos Vicente-Gómez Francisco Vargas-Gasca Fernando Anaya-Velázquez Itzel Páramo-Pérez Ángeles Rangel-Serrano Patricia Cuéllar-Mata Naurú Idalia Vargas-Maya Bernardo Franco |
| author_sort | Felipe Padilla-Vaca |
| collection | DOAJ |
| description | The complex metabolism of Escherichia coli has been extensively studied, including its response to oxygen availability. The ArcA/B two-component system (TCS) is the key regulator for the transition between these two environmental conditions and has been thoroughly characterized using genetic and biochemical approaches. Still, to date, limited structural data is available. The breakthrough provided by AlphaFold2 in 2021 has brought a reliable tool to the scientific community for assessing the structural features of complex proteins. In this report, we analyzed the structural aspects of the ArcA/B TCS using AlphaFold2 models. The models are consistent with the experimentally determined structures of ArcB kinase. The predicted structure of the dimeric form of ArcB is consistent with the extensive genetic and biochemical data available regarding mechanistic signal perception and regulation. The predicted interaction of the dimeric form of ArcB with its cognate response regulator (ArcA) is also consistent with both the forward and reverse phosphotransfer mechanisms. The ArcB model was used to detect putative binding cavities to anaerobic metabolites, encouraging testing of these predictions experimentally. Finally, the highly accurate models of other ArcB homologs suggest that different experimental approaches are needed to determine signal perception in kinases lacking the PAS domain. Overall, ArcB is a kinase with features that need further testing, especially in determining its crystal structure under different conditions. |
| first_indexed | 2024-03-09T07:05:33Z |
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| id | doaj.art-d1b97904c6454899a906ec6934b597f5 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:05:33Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-d1b97904c6454899a906ec6934b597f52023-12-03T09:36:29ZengPeerJ Inc.PeerJ2167-83592023-10-0111e1630910.7717/peerj.16309Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcAFelipe Padilla-Vaca0Javier de la Mora1Rodolfo García-Contreras2Jorge Humberto Ramírez-Prado3Marcos Vicente-Gómez4Francisco Vargas-Gasca5Fernando Anaya-Velázquez6Itzel Páramo-Pérez7Ángeles Rangel-Serrano8Patricia Cuéllar-Mata9Naurú Idalia Vargas-Maya10Bernardo Franco11Biology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoGenética Molecular, Instituto de Fisiología Celular, Mexico City, Mexico City, MéxicoFacultad de Médicina, Universidad Nacional Autónoma de México, Mexico City, Mexico City, MexicoUnidad de Biotecnología, Centro de Investigación Científica de Yucatán, A. C., Mérida, Yucatán, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoBiology, Universidad de Guanajuato, Guanajuato, Guanajuato, MéxicoThe complex metabolism of Escherichia coli has been extensively studied, including its response to oxygen availability. The ArcA/B two-component system (TCS) is the key regulator for the transition between these two environmental conditions and has been thoroughly characterized using genetic and biochemical approaches. Still, to date, limited structural data is available. The breakthrough provided by AlphaFold2 in 2021 has brought a reliable tool to the scientific community for assessing the structural features of complex proteins. In this report, we analyzed the structural aspects of the ArcA/B TCS using AlphaFold2 models. The models are consistent with the experimentally determined structures of ArcB kinase. The predicted structure of the dimeric form of ArcB is consistent with the extensive genetic and biochemical data available regarding mechanistic signal perception and regulation. The predicted interaction of the dimeric form of ArcB with its cognate response regulator (ArcA) is also consistent with both the forward and reverse phosphotransfer mechanisms. The ArcB model was used to detect putative binding cavities to anaerobic metabolites, encouraging testing of these predictions experimentally. Finally, the highly accurate models of other ArcB homologs suggest that different experimental approaches are needed to determine signal perception in kinases lacking the PAS domain. Overall, ArcB is a kinase with features that need further testing, especially in determining its crystal structure under different conditions.https://peerj.com/articles/16309.pdfArcBTwo-component systemsProtein modelingAlphaFold2Signaling mechanismKinase regulation |
| spellingShingle | Felipe Padilla-Vaca Javier de la Mora Rodolfo García-Contreras Jorge Humberto Ramírez-Prado Marcos Vicente-Gómez Francisco Vargas-Gasca Fernando Anaya-Velázquez Itzel Páramo-Pérez Ángeles Rangel-Serrano Patricia Cuéllar-Mata Naurú Idalia Vargas-Maya Bernardo Franco Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA PeerJ ArcB Two-component systems Protein modeling AlphaFold2 Signaling mechanism Kinase regulation |
| title | Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA |
| title_full | Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA |
| title_fullStr | Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA |
| title_full_unstemmed | Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA |
| title_short | Theoretical study of ArcB and its dimerization, interaction with anaerobic metabolites, and activation of ArcA |
| title_sort | theoretical study of arcb and its dimerization interaction with anaerobic metabolites and activation of arca |
| topic | ArcB Two-component systems Protein modeling AlphaFold2 Signaling mechanism Kinase regulation |
| url | https://peerj.com/articles/16309.pdf |
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