MbnH is a diheme MauG-like protein associated with microbial copper homeostasis

Grace E. Kenney, Laura M.K. Dassama, Anastasia C. Manesis, Matthew O. Ross, Siyu Chen, Brian M. Hoffman, Amy C. Rosenzweig*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Methanobactins (Mbns) are ribosomally-produced, post-translationally modified peptidic copper-binding natural products produced under conditions of copper limitation. Genes encoding Mbn bio-synthetic and transport proteins have been identified in a wide variety of bacteria, indicating a broader role for Mbns in bacterial metal homeostasis. Many of the genes in the Mbn operons have been assigned functions, but two genes usually present, mbnP and mbnH, encode uncharacterized proteins predicted to reside in the periplasm. MbnH belongs to the bacterial diheme cytochrome c peroxidase (bCcP)/MauG protein family, and MbnP contains no domains of known function. Here, we performed a detailed bioinformatic analysis of both proteins and have biochemically characterized MbnH from Methylosinus (Ms.) trichosporium OB3b. We note that the mbnH and mbnP genes typically co-occur and are located proximal to genes associated with microbial copper homeostasis. Our bioinformatics analysis also revealed that the bCcP/MauG family is significantly more diverse than originally appreciated, and that MbnH is most closely related to the MauG subfamily. A 2.6 Å resolution structure of Ms. trichosporium OB3b MbnH combined with spectroscopic data and peroxidase activity assays provided evidence that MbnH indeed more closely resembles MauG than bCcPs, although its redox properties are significantly different from those of MauG. The overall similarity of MbnH to MauG suggests that MbnH could post-translationally modify a macromolecule, such as internalized CuMbn or its uncharacterized partner protein, MbnP. Our results indicate that MbnH is a MauG-like diheme protein that is likely involved in microbial copper homeostasis and represents a new family within the bCcP/MauG superfamily.

Original languageEnglish (US)
Pages (from-to)16141-16151
Number of pages11
JournalJournal of Biological Chemistry
Volume294
Issue number44
DOIs
StatePublished - Nov 1 2019

Funding

This work was supported by National Institutes of Health Grants GM118035 (to A. C. R.), GM111097 (to B. M. H.), and F32GM110934 (to L. M. K. D.), and a Burroughs Wellcome Fund Postdoctoral Enrichment Program grant (to L. M. K. D.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This article contains Figs. S1–S16 and Files S1–S5. The atomic coordinates and structure factors (code 6E1C) have been deposited in the Protein Data Bank (http://wwpdb.org/). 1 Present address: Dept. of Chemistry and Chemical Biology, Harvard Univer-sity, Cambridge, MA 02138. 2 Both authors contributed equally to this work. 3 Present address: ChEM-H Institute and Dept. of Chemistry, Stanford Univer-sity, Stanford, CA 94305. 4To whom correspondence should be addressed. Tel.: 847-467-5301; Fax: 847-467-6489; E-mail: [email protected]. This work was supported by National Institutes of Health Grants GM118035 (to A. C. R.), GM111097 (to B. M. H.), and F32GM110934 (to L. M. K. D.), and a Burroughs Wellcome Fund Postdoctoral Enrichment Program grant (to L. M. K. D.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments-This work used resources of the Advanced Photon Source, a United States Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor Grant 085P1000817. Acknowledgments—This work used resources of the Advanced Photon Source, a United States Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor Grant 085P1000817.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'MbnH is a diheme MauG-like protein associated with microbial copper homeostasis'. Together they form a unique fingerprint.

Cite this