Studying GGDEF Domain in the Act: Minimize Conformational Frustration to Prevent Artefacts

Federico Mantoni; Chiara Scribani Rossi; Alessandro Paiardini; Adele Di Matteo; Loredana Cappellacci; Riccardo Petrelli; Massimo Ricciutelli; Alessio Paone; Francesca Cutruzzolà; Giorgio Giardina; Serena Rinaldo

doi:10.3390/life11010031

Life (Jan 2021)

Studying GGDEF Domain in the Act: Minimize Conformational Frustration to Prevent Artefacts

Federico Mantoni,
Chiara Scribani Rossi,
Alessandro Paiardini,
Adele Di Matteo,
Loredana Cappellacci,
Riccardo Petrelli,
Massimo Ricciutelli,
Alessio Paone,
Francesca Cutruzzolà,
Giorgio Giardina,
Serena Rinaldo

Affiliations

Federico Mantoni: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Chiara Scribani Rossi: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Alessandro Paiardini: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Adele Di Matteo: Institute of Molecular Biology and Pathology, CNR, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Loredana Cappellacci: Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Riccardo Petrelli: Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Massimo Ricciutelli: Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Alessio Paone: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Francesca Cutruzzolà: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Giorgio Giardina: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy
Serena Rinaldo: Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy

DOI: https://doi.org/10.3390/life11010031
Journal volume & issue: Vol. 11, no. 1
p. 31

Abstract

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GGDEF-containing proteins respond to different environmental cues to finely modulate cyclic diguanylate (c-di-GMP) levels in time and space, making the allosteric control a distinctive trait of the corresponding proteins. The diguanylate cyclase mechanism is emblematic of this control: two GGDEF domains, each binding one GTP molecule, must dimerize to enter catalysis and yield c-di-GMP. The need for dimerization makes the GGDEF domain an ideal conformational switch in multidomain proteins. A re-evaluation of the kinetic profile of previously characterized GGDEF domains indicated that they are also able to convert GTP to GMP: this unexpected reactivity occurs when conformational issues hamper the cyclase activity. These results create new questions regarding the characterization and engineering of these proteins for in solution or structural studies.

Published in Life

ISSN: 2075-1729 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science
Website: http://www.mdpi.com/journal/life

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