Structural analysis of the manganese transport regulator MntR from Bacillus halodurans in apo and manganese bound forms


Autoři: Myeong Yeon Lee aff001;  Dong Won Lee aff001;  Hyun Kyu Joo aff001;  Kang Hwa Jeong aff001;  Jae Young Lee aff001
Působiště autorů: Department of Life Science, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224689

Souhrn

The manganese transport regulator MntR is a metal-ion activated transcriptional repressor of manganese transporter genes to maintain manganese ion homeostasis. MntR, a member of the diphtheria toxin repressor (DtxR) family of metalloregulators, selectively responds to Mn2+ and Cd2+ over Fe2+, Co2+ and Zn2+. The DtxR/MntR family members are well conserved transcriptional repressors that regulate the expression of metal ion uptake genes by sensing the metal ion concentration. MntR functions as a homo-dimer with one metal ion binding site per subunit. Each MntR subunit contains two domains: an N-terminal DNA binding domain, and a C-terminal dimerization domain. However, it lacks the C-terminal SH3-like domain of DtxR/IdeR. The metal ion binding site of MntR is located at the interface of the two domains, whereas the DtxR/IdeR subunit contains two metal ion binding sites, the primary and ancillary sites, separated by 9 Å. In this paper, we reported the crystal structures of the apo and Mn2+-bound forms of MntR from Bacillus halodurans, and analyze the structural basis of the metal ion binding site. The crystal structure of the Mn2+-bound form is almost identical to the apo form of MntR. In the Mn2+-bound structure, one subunit contains a binuclear cluster of manganese ions, the A and C sites, but the other subunit forms a mononuclear complex. Structural data about MntR from B. halodurans supports the previous hypothesizes about manganese-specific activation mechanism of MntR homologues.

Klíčová slova:

Crystal structure – Crystals – Dimerization – Glycerol – Hydrogen bonding – Magnesium – Manganese – Protein domains


Zdroje

1. Rosenzweig AC. Metallochaperones: Bind and deliver. Chemistry and Biology. 2002. doi: 10.1016/S1074-5521(02)00156-4

2. Papp-Wallace KM, Maguire ME. Manganese Transport and the Role of Manganese in Virulence. Annual Review of Microbiology. 2006;60: 187–209. doi: 10.1146/annurev.micro.60.080805.142149 16704341

3. Torrents E. Ribonucleotide reductases: essential enzymes for bacterial life. Frontiers in Cellular and Infection Microbiology. 2014;4: 1–9.

4. Kliegman JI, Griner SL, Helmann JD, Brennan RG, Glasfeld A. Structural basis for the metal-selective activation of the manganese transport regulator of Bacillus subtilis. Biochemistry. 2006; doi: 10.1021/bi0524215 16533030

5. McGuire AM, Cuthbert BJ, Ma Z, Grauer-Gray KD, Brunjes Brophy M, Spear KA, et al. Roles of the A and C sites in the manganese-specific activation of MntR. Biochemistry. 2013; doi: 10.1021/bi301550t 23298157

6. Helmann JD. Specificity of metal sensing: Iron and manganese homeostasis in bacillus subtilis. Journal of Biological Chemistry. 2014. doi: 10.1074/jbc.R114.587071 25160631

7. Tanaka T, Shinkai A, Bessho Y, Kumarevel T, Yokoyama S. Crystal structure of the manganese transport regulatory protein from Escherichia coli. Proteins: Structure, Function and Bioinformatics. 2009; doi: 10.1002/prot.22541 19701940

8. Glasfeld A, Guedon E, Helmann JD, Brennan RG. Structure of the manganese-bound manganese transport regulator of Bacillus subtilis. Nature Structural Biology. 2003; doi: 10.1038/nsb951 12847518

9. Huang X, Shin JH, Pinochet-Barros A, Su TT, Helmann JD. Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems. Molecular Microbiology. 2017; doi: 10.1111/mmi.13554 27748968

10. Chandrangsu P, Rensing C, Helmann JD. Metal homeostasis and resistance in bacteria. Nature Reviews Microbiology. 2017. doi: 10.1038/nrmicro.2017.15 28344348

11. Que Q, Helmann JD. Manganese homestasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins. Molecular Microbiology. 2000; doi: 10.1046/j.1365-2958.2000.01811.x

12. Cong X, Yuan Z, Wang Z, Wei B, Xu S, Wang J. Crystal structures of manganese-dependent transcriptional repressor MntR (Rv2788) from Mycobacterium tuberculosis in apo and manganese bound forms. Biochemical and Biophysical Research Communications. 2018; doi: 10.1016/j.bbrc.2018.05.005 29730293

13. Schiering N, Tao X, Zeng H, Murphy JR, Petsko GA, Ringe D. Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae. Proceedings of the National Academy of Sciences of the United States of America. 1995; doi: 10.1073/pnas.92.21.9843 7568230

14. Pohl E, Holmes RK, Hol WGJ. Crystal structure of the iron-dependent regulator (IdeR) from Mycobacterium tuberculosis shows both metal binding sites fully occupied. Journal of Molecular Biology. 1999; doi: 10.1006/jmbi.1998.2339 9887269

15. White A, Ding X, VanderSpek JC, Murphy JR, Ringe D. Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex. Nature. 1998;394: 502–506. doi: 10.1038/28893 9697776

16. Qiu X, Verlinde CL, Zhang S, Schmitt MP, Holmes RK, Hol WG. Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors. Structure. 1995; doi: 10.1016/S0969-2126(01)00137-X

17. Pandey R, Russo R, Ghanny S, Huang X, Helmann J, Rodriguez GM. MntR(Rv2788): A transcriptional regulator that controls manganese homeostasis in Mycobacterium tuberculosis. Molecular Microbiology. 2015; doi: 10.1111/mmi.13207 26337157

18. DeWitt MA, Kliegman JI, Helmann JD, Brennan RG, Farrens DL, Glasfeld A. The Conformations of the Manganese Transport Regulator of Bacillus subtilis in its Metal-free State. Journal of Molecular Biology. 2007; doi: 10.1016/j.jmb.2006.10.080 17118401

19. Lieser SA, Davis TC, Helmann JD, Cohen SM. DNA-Binding and Oligomerization Studies of the Manganese(II) Metalloregulatory Protein MntR from Bacillus subtilis. Biochemistry. 2003; doi: 10.1021/bi0350248 14580210

20. Otwinowski Z, Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology. 1997; doi: 10.1016/S0076-6879(97)76066-X

21. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. Journal of Applied Crystallography. 2007; doi: 10.1107/S0021889807021206 19461840

22. Emsley P, Cowtan K. Coot: Model-building tools for molecular graphics. Acta Crystallographica Section D: Biological Crystallography. 2004; doi: 10.1107/S0907444904019158 15572765

23. Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, et al. MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D: Biological Crystallography. 2010; doi: 10.1107/S0907444909042073 20057044

24. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Molecular Systems Biology. 2011; doi: 10.1038/msb.2011.75 21988835

25. Holm L, Laakso LM. Dali server update. Nucleic acids research. 2016; doi: 10.1093/nar/gkw357 27131377

26. Pohl E, Holmes RK, Hol WGJ. Motion of the DNA-binding domain with respect to the core of the diphtheria toxin repressor (DtxR) revealed in the crystal structures of apo- and holo-DtxR. Journal of Biological Chemistry. 1998; doi: 10.1074/jbc.273.35.22420 9712865

27. Wisedchaisri G, Holmes RK, Hol WGJ. Crystal structure of an IdeR-DNA complex reveals a conformational change in activated IdeR for base-specific interactions. Journal of Molecular Biology. 2004; doi: 10.1016/j.jmb.2004.07.083 15351642

28. Yeo HK, Park YW, Lee JY. Structural analysis and insight into metal-ion activation of the iron-dependent regulator from Thermoplasma acidophilum. Acta Crystallographica Section D: Biological Crystallography. 2014; doi: 10.1107/S1399004714004118 24816097


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2019 Číslo 11