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Structure of the manganese-bound manganese transport regulator of Bacillus subtilis

Nature Structural & Molecular Biology volume 10, pages 652–657 (2003)Cite this article

Abstract

The Bacillus subtilis manganese transport regulator, MntR, binds Mn2+ as an effector and is a repressor of transporters that import manganese. A member of the diphtheria toxin repressor (DtxR) family of metalloregulatory proteins, MntR exhibits selectivity for Mn2+ over Fe2+. Replacement of a metal-binding residue, Asp8, with methionine (D8M) relaxes this specificity. We report here the X-ray crystal structures of wild-type MntR and the D8M mutant bound to manganese with 1.75 Å and 1.61 Å resolution, respectively. The 142-residue MntR homodimer has substantial structural similarity to the 226-residue DtxR but lacks the C-terminal SH3-like domain of DtxR. The metal-binding pockets of MntR and DtxR are substantially different. The cation-to-cation distance between the two manganese ions bound by MntR is 3.3 Å, whereas that between the metal ions bound by DtxR is 9 Å. D8M binds only a single Mn2+ per monomer, owing to alteration of the metal-binding site. The sole retained metal site adopts pseudo-hexacoordinate geometry rather than the pseudo-heptacoordinate geometry of the MntR metal sites.

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Figure 1: Structures of manganese-bound wild-type MntR and the D8M mutant.
Figure 2: Stereo view of a σA-weighted Fo − Fc omit electron density map of the metal-binding region of MntR.
Figure 3: Comparison of wild-type MntR and D8M metal-binding sites.
Figure 4: Overlay of metal-binding regions of MntR (colored by atom type as in Fig. 3b) and cobalt-bound IdeR (PDB entry 1FX7; green).

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Acknowledgements

We thank M.A. Schumacher for help with data collection and K.J. Newberry for assistance with refinement and model building. This work was supported in part by the Oregon Medical Research Foundation (A.G.) and grants from the US National Institutes of Health (NIH) (R.G.B. and J.D.H.). Portions of this research were carried out at the Stanford Synchrotron Radiation Laboratory (SSRL), operated by Stanford University on behalf of the US Department of Energy (DOE), Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the DOE, Office of Biological and Environmental Research, and by the US NIH, National Center for Research Resources, Biomedical Technology Program, and the National Institute of General Medical Sciences.

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  1. Emmanuel Guedon

    Present address: Laboratoire des Sciences du Génie Chimique, UPR-CNRS 6811, ENSAIA-INPL, 2 Avenue de la Forêt de Haye, BP 172, 54505, Vandoeuvre-lès-Nancy, France

Authors and Affiliations

  1. Department of Chemistry, Reed College, 3203 SE Woodstock Blvd., Portland, 97202, Oregon, USA

    Arthur Glasfeld

  2. Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, 97201, Oregon, USA

    Arthur Glasfeld & Richard G Brennan

  3. Department of Microbiology, 175A Wing Hall, Cornell University, Ithaca, 14853, New York, USA

    Emmanuel Guedon & John D Helmann

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Correspondence to Arthur Glasfeld or Richard G Brennan.

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Glasfeld, A., Guedon, E., Helmann, J. et al. Structure of the manganese-bound manganese transport regulator of Bacillus subtilis. Nat Struct Mol Biol 10, 652–657 (2003). https://doi.org/10.1038/nsb951

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