Reconstitution of the Arginyltransferase (ATE1) Iron-Sulfur Cluster

Methods Mol Biol. 2023:2620:209-217. doi: 10.1007/978-1-0716-2942-0_23.

Abstract

As global regulators of eukaryotic homeostasis, arginyltransferases (ATE1s) have essential functions within the cell. Thus, the regulation of ATE1 is paramount. It was previously postulated that ATE1 was a hemoprotein and that heme was an operative cofactor responsible for enzymatic regulation and inactivation. However, we have recently shown that ATE1 instead binds an iron-sulfur ([Fe-S]) cluster that appears to function as an oxygen sensor to regulate ATE1 activity. As this cofactor is oxygen-sensitive, purification of ATE1 in the presence of O2 results in cluster decomposition and loss. Here, we describe an anoxic chemical reconstitution protocol to assemble the [Fe-S] cluster cofactor in Saccharomyces cerevisiae ATE1 (ScATE1) and Mus musculus ATE1 isoform 1 (MmATE1-1).

Keywords: Anoxic reconstitution; Arginylation; Arginyltransferases; Chemical reconstitution; Ferrozine assay; Iron-sulfur clusters.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminoacyltransferases* / chemistry
  • Animals
  • Iron-Sulfur Proteins* / metabolism
  • Mice
  • Protein Isoforms / metabolism
  • Proteolysis
  • Saccharomyces cerevisiae / metabolism

Substances

  • arginyltransferase
  • Protein Isoforms
  • Aminoacyltransferases
  • Iron-Sulfur Proteins