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

Cell Rep. 2022 May 17;39(7):110834. doi: 10.1016/j.celrep.2022.110834.

Abstract

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.

Keywords: CBWD; COG0523; CP: Molecular biology; CobW; GTPase; MetAP; NME; insertase; nutrient limitation; zinc homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Guanosine Triphosphate
  • Humans
  • Metals / metabolism
  • Methionine
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / physiology
  • Transferases* / physiology
  • Zinc* / metabolism

Substances

  • Aminopeptidases
  • Guanosine Triphosphate
  • Metals
  • METAP1 protein, human
  • Methionine
  • Saccharomyces cerevisiae Proteins
  • Transferases
  • Zinc
  • ZNG1B protein, human
  • ZNG1 protein, S cerevisiae