Molecular Dynamics Simulations Reveal Differences in the Conformational Stability of FtsZs Derived from Staphylococcus Aureus and Bacillus Subtilis

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jul 11

PMID 38992051

Authors

Taichi Takasawa

Takashi Matsui

Go Watanabe

Yoshio Kodera

Affiliations

Soon will be listed here.

Abstract

FtsZ is highly conserved among bacteria and plays an essential role in bacterial cell division. The tense conformation of FtsZ bound to GTP assembles into a straight filament via head-to-tail associations, and then the upper subunit of FtsZ hydrolyzes GTP bound to the lower FtsZ subunit. The subunit with GDP bound disassembles accompanied by a conformational change in the subunit from the tense to relaxed conformation. Although crystal structures of FtsZ derived from several bacterial species have been determined, the conformational change from the relaxed to tense conformation has only been observed in Staphylococcus aureus FtsZ (SaFtsZ). Recent cryo-electron microscopy analyses revealed the three-dimensional reconstruction of the protofilament, in which tense molecules assemble via head-to-tail associations. However, the lower resolution of the protofilament suggested that the flexibility of the FtsZ protomers between the relaxed and tense conformations caused them to form in less-strict alignments. Furthermore, this flexibility may also prevent FtsZs other than SaFtsZ from crystalizing in the tense conformation, suggesting that the flexibility of bacterial FtsZs differs. In this study, molecular dynamics simulations were performed using SaFtsZ and Bacillus subtilis FtsZ in several situations, which suggested that different features of the FtsZs affect their conformational stability.

References

Huecas S, Araujo-Bazan L, Ruiz F, Ruiz-Avila L, Martinez R, Escobar-Pena A . Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery. J Med Chem. 2021; 64(9):5730-5745. PMC: 8478281. DOI: 10.1021/acs.jmedchem.0c02207. View

Fujita J, Sugiyama S, Terakado H, Miyazaki M, Ozawa M, Ueda N . Dynamic Assembly/Disassembly of FtsZ Visualized by High-Speed Atomic Force Microscopy. Int J Mol Sci. 2021; 22(4). PMC: 7914567. DOI: 10.3390/ijms22041697. View

Fujita J, Maeda Y, Mizohata E, Inoue T, Kaul M, Parhi A . Structural Flexibility of an Inhibitor Overcomes Drug Resistance Mutations in Staphylococcus aureus FtsZ. ACS Chem Biol. 2017; 12(7):1947-1955. PMC: 5705026. DOI: 10.1021/acschembio.7b00323. View

Heo L, Feig M . Multi-state modeling of G-protein coupled receptors at experimental accuracy. Proteins. 2022; 90(11):1873-1885. PMC: 9561049. DOI: 10.1002/prot.26382. View

Haydon D, Stokes N, Ure R, Galbraith G, Bennett J, Brown D . An inhibitor of FtsZ with potent and selective anti-staphylococcal activity. Science. 2008; 321(5896):1673-5. DOI: 10.1126/science.1159961. View

Fujita J, Amesaka H, Yoshizawa T, Hibino K, Kamimura N, Kuroda N . Structures of a FtsZ single protofilament and a double-helical tube in complex with a monobody. Nat Commun. 2023; 14(1):4073. PMC: 10333351. DOI: 10.1038/s41467-023-39807-5. View

Matsui T, Yamane J, Mogi N, Yamaguchi H, Takemoto H, Yao M . Structural reorganization of the bacterial cell-division protein FtsZ from Staphylococcus aureus. Acta Crystallogr D Biol Crystallogr. 2012; 68(Pt 9):1175-88. DOI: 10.1107/S0907444912022640. View

Fu H, Chen H, Blazhynska M, Goulard Coderc de Lacam E, Szczepaniak F, Pavlova A . Accurate determination of protein:ligand standard binding free energies from molecular dynamics simulations. Nat Protoc. 2022; 17(4):1114-1141. PMC: 10082674. DOI: 10.1038/s41596-021-00676-1. View

Lu C, Reedy M, Erickson H . Straight and curved conformations of FtsZ are regulated by GTP hydrolysis. J Bacteriol. 1999; 182(1):164-70. PMC: 94253. DOI: 10.1128/JB.182.1.164-170.2000. View

10.

Matsui T, Kojitani E, Takasawa T, Suto A, Tamari A, Watanabe G . Assessment of inconsistencies in the solvent-accessible surfaces of proteins between crystal structures and solution structures observed by LC-MS. Biochem Biophys Res Commun. 2022; 640:97-104. DOI: 10.1016/j.bbrc.2022.11.094. View

11.

Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T . SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 2014; 42(Web Server issue):W252-8. PMC: 4086089. DOI: 10.1093/nar/gku340. View

12.

Wagstaff J, Planelles-Herrero V, Sharov G, Alnami A, Kozielski F, Derivery E . Diverse cytomotive actins and tubulins share a polymerization switch mechanism conferring robust dynamics. Sci Adv. 2023; 9(13):eadf3021. PMC: 10058229. DOI: 10.1126/sciadv.adf3021. View

13.

Strodel B . Energy Landscapes of Protein Aggregation and Conformation Switching in Intrinsically Disordered Proteins. J Mol Biol. 2021; 433(20):167182. DOI: 10.1016/j.jmb.2021.167182. View

14.

Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis J, Dror R . Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins. 2010; 78(8):1950-8. PMC: 2970904. DOI: 10.1002/prot.22711. View

15.

Ferrer-Gonzalez E, Fujita J, Yoshizawa T, Nelson J, Pilch A, Hillman E . Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens. Sci Rep. 2019; 9(1):20092. PMC: 6934700. DOI: 10.1038/s41598-019-56557-x. View

16.

Wang J, Wolf R, Caldwell J, Kollman P, Case D . Development and testing of a general amber force field. J Comput Chem. 2004; 25(9):1157-74. DOI: 10.1002/jcc.20035. View

17.

Margolin W . FtsZ and the division of prokaryotic cells and organelles. Nat Rev Mol Cell Biol. 2005; 6(11):862-71. PMC: 4757588. DOI: 10.1038/nrm1745. View

18.

Fujita J, Harada R, Maeda Y, Saito Y, Mizohata E, Inoue T . Identification of the key interactions in structural transition pathway of FtsZ from Staphylococcus aureus. J Struct Biol. 2017; 198(2):65-73. DOI: 10.1016/j.jsb.2017.04.008. View

19.

Adams D, Errington J . Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nat Rev Microbiol. 2009; 7(9):642-53. DOI: 10.1038/nrmicro2198. View

20.

Elsen N, Lu J, Parthasarathy G, Reid J, Sharma S, Soisson S . Mechanism of action of the cell-division inhibitor PC190723: modulation of FtsZ assembly cooperativity. J Am Chem Soc. 2012; 134(30):12342-5. DOI: 10.1021/ja303564a. View