Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase
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The evolution of zinc (Zn) as a protein cofactor altered the functional landscape of biology, but dependency on Zn also created an Achilles' heel, necessitating adaptive mechanisms to ensure Zn availability to proteins. A debated strategy is whether metallochaperones exist to prioritize essential Zn-dependent proteins. Here, we present evidence for a conserved family of putative metal transferases in human and fungi, which interact with Zn-dependent methionine aminopeptidase type I (MetAP1/Map1p/Fma1). Deletion of the putative metal transferase in Saccharomyces cerevisiae ( ZNG1 ; formerly YNR029c ) leads to defective Map1p function and a Zn-deficiency growth defect. In vitro , Zng1p can transfer Zn 2+ or Co 2+ to apo-Map1p, but unlike characterized copper chaperones, transfer is dependent on GTP hydrolysis. Proteomics reveal mis-regulation of the Zap1p transcription factor regulon because of loss of ZNG1 and Map1p activity, suggesting that Zng1p is required to avoid a compounding effect of Map1p dysfunction on survival during Zn limitation.
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Thiol-dependent ligand exchange reactions underlie the ability of COG0523 family proteins to function as GTP-activated Zn2+ metallochaperones to direct the flow of Zn2+ to the most important client proteins under conditions of Zn limitation.
“Thiol-dependent ligand exchange reactions also underlie the ability of COG0523 family proteins to function as GTP-activated Zn2+ metallochaperones to direct the flow of Zn2+ to the most important client proteins under conditions of Zn limitation.213−217”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [216]
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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
- Authors
- Pasquini, M., Grosjean, N., Hixson, K. K., Nicora, C. D., Yee, E. F., Lipton, M., Blaby, I. K., Haley, J. D., & Blaby-Haas, C. E.
- Affiliations
- Brookhaven National Laboratory (US)
- Pacific Northwest National Laboratory (US)
- Stony Brook University (US)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 39
- Issue
- 7
- Pages
- 110834
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4280627703
- Cited by
- 55
- References
- 5
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 10 · 2023: 13 · 2022: 4
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy
- Office of Science
- Biological and Environmental Research
- Brookhaven National Laboratory (21-038)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- metallochaperone, GTP hydrolysis, zinc deficiency, zinc availability, Saccharomyces cerevisiae
- MeSH terms
- Aminopeptidases, Guanosine Triphosphate, Humans, Metals, Methionine, Saccharomyces cerevisiae, Transferases, Zinc, Nitrogenous Group Transferases, GTP Phosphohydrolases, Saccharomyces cerevisiae Proteins
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