Cell Reports
Volume 39, Issue 7, 17 May 2022, 110834
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Article
Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase

https://doi.org/10.1016/j.celrep.2022.110834Get rights and content
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Highlights

  • Zng1p is needed for Map1p activity, a function that is essential in zinc deficiency

  • The N-terminal zinc-finger domain of Map1p is critical for the interaction with Zng1p

  • Zinc transfer to Map1p by Zng1p is dependent on GTP hydrolysis

  • Zng1p is required for proper expression of the zinc-deficiency response

Summary

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 Zn2+ or Co2+ 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.

Research topic(s)

CP: Molecular biology

Keywords

MetAP
insertase
NME
GTPase
zinc homeostasis
nutrient limitation
COG0523
CobW
CBWD

Data and code availability

  • Raw data from the TMT-based proteomics have been deposited at MassIVE Repository and are publicly available as of the date of publication. The accession number is listed in the key resources table. All other data reported in this paper will be shared by the lead contact upon request.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

7

Present address: US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA

8

These authors contributed equally

9

Lead contact