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Title: Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase

Journal Article · · Cell Reports
ORCiD logo [1];  [1];  [2];  [2]; ORCiD logo [3];  [2]; ORCiD logo [1];  [4]; ORCiD logo [5]
  1. Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
  4. Stony Brook Univ., NY (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., NY (United States)

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 due to 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 Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Laboratory Directed Research and Development (LDRD) Program
Grant/Contract Number:
SC0012704; AC02-05CH11231
OSTI ID:
1868509
Alternate ID(s):
OSTI ID: 1882662; OSTI ID: 1925193
Report Number(s):
BNL-222969-2022-JAAM
Journal Information:
Cell Reports, Journal Name: Cell Reports Journal Issue: 7 Vol. 39; ISSN 2211-1247
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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