TerC proteins function during protein secretion to metalate exoenzymes
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Abstract
Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported metalloenzymes are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein export and a greatly reduced level of manganese (Mn) in the secreted proteome. MeeF and MeeY copurify with proteins of the general secretory pathway, and in their absence the FtsH membrane protease is essential for viability. MeeF and MeeY are also required for efficient function of the Mn 2+ -dependent lipoteichoic acid synthase (LtaS), a membrane-localized enzyme with an extracytoplasmic active site. Thus, MeeF and MeeY, representative of the widely conserved TerC family of membrane transporters, function in the co-translocational metalation of Mn 2+ -dependent membrane and extracellular enzymes.
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The bulk of the quota for manganese and iron is devoted to intracellular enzymes, with a variable fraction partitioned to the membrane or to extracellular enzymes, and the latter may require dedicated maturation pathways.
“The bulk of the quota for manganese and iron is devoted to intracellular enzymes (Figure 3), with a variable fraction partitioned to the membrane (e.g., respiratory complexes) or to extracellular enzymes. The latter may require dedicated pathways for their maturation.95,96”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [95]
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Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701 · cited 1× · see citing works
“The role of TerC proteins in exoprotein metalation is likely important for bacterial pathogens that often face metal limitation due to host-imposed nutritional immunity 19,76 .”
Protein export through the bacterial Sec pathway
Tsirigotaki, A., De Geyter, J., Šoštaric´, N., Economou, A., & Karamanou, S. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.161 · Cited by 447 · see citing works
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Metals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
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- Authors
- He, B., Sachla, A. J., & Helmann, J. D.
- Affiliations
- Cornell University (US)
- Corresponding author
- Helmann, John D.
- Venue
- Nature Communications
- Published
- 2023-10-04
- Volume
- 14
- Issue
- 1
- Pages
- 6186-6186
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10550928
- OpenAlex
- W4387343660
- Cited by
- 26
- References
- 4
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc)
- PubMed Central (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R35GM122461)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- MEEF, manganese, general secretion pathway, Sec-dependent secretion, LTA, Bacillus subtilis, membrane transporters
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