Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase
Miriam Pasquini,
Nicolas Grosjean,
Kim K. Hixson,
Carrie D. Nicora,
Estella F. Yee,
Mary Lipton,
Ian K. Blaby,
John D. Haley,
Crysten E. Blaby-Haas
Affiliations
Miriam Pasquini
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
Nicolas Grosjean
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
Kim K. Hixson
The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Carrie D. Nicora
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Estella F. Yee
National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, NY 11973, USA
Mary Lipton
The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Ian K. Blaby
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
John D. Haley
Department of Pathology and Biological Mass Spectrometry Facility, Stony Brook University, Stony Brook, NY 11794, USA
Crysten E. Blaby-Haas
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA; Corresponding author
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.
