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Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis.
Weiss, Andy; Murdoch, Caitlin C; Edmonds, Katherine A; Jordan, Matthew R; Monteith, Andrew J; Perera, Yasiru R; Rodríguez Nassif, Aslin M; Petoletti, Amber M; Beavers, William N; Munneke, Matthew J; Drury, Sydney L; Krystofiak, Evan S; Thalluri, Kishore; Wu, Hongwei; Kruse, Angela R S; DiMarchi, Richard D; Caprioli, Richard M; Spraggins, Jeffrey M; Chazin, Walter J; Giedroc, David P; Skaar, Eric P.
Afiliação
  • Weiss A; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Murdoch CC; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Edmonds KA; Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
  • Jordan MR; Department of Chemistry, Indiana University, Bloomington, IN 47405, USA; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA.
  • Monteith AJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Perera YR; Departments of Biochemistry and Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA.
  • Rodríguez Nassif AM; Departments of Biochemistry and Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA.
  • Petoletti AM; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Beavers WN; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Munneke MJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Drury SL; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Krystofiak ES; Cell Imaging Shared Resource, Vanderbilt University, Nashville, TN 37232, USA.
  • Thalluri K; Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
  • Wu H; Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
  • Kruse ARS; Departments of Chemistry and Biochemistry, Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA.
  • DiMarchi RD; Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
  • Caprioli RM; Departments of Chemistry and Biochemistry, Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA.
  • Spraggins JM; Departments of Chemistry and Biochemistry, Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
  • Chazin WJ; Departments of Biochemistry and Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA.
  • Giedroc DP; Department of Chemistry, Indiana University, Bloomington, IN 47405, USA; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA. Electronic address: giedroc@indiana.edu.
  • Skaar EP; Department of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: eric.skaar@vumc.org.
Cell ; 185(12): 2148-2163.e27, 2022 06 09.
Article em En | MEDLINE | ID: mdl-35584702
ABSTRACT
Zinc (Zn) is an essential micronutrient and cofactor for up to 10% of proteins in living organisms. During Zn limitation, specialized enzymes called metallochaperones are predicted to allocate Zn to specific metalloproteins. This function has been putatively assigned to G3E GTPase COG0523 proteins, yet no Zn metallochaperone has been experimentally identified in any organism. Here, we functionally characterize a family of COG0523 proteins that is conserved across vertebrates. We identify Zn metalloprotease methionine aminopeptidase 1 (METAP1) as a COG0523 client, leading to the redesignation of this group of COG0523 proteins as the Zn-regulated GTPase metalloprotein activator (ZNG1) family. Using biochemical, structural, genetic, and pharmacological approaches across evolutionarily divergent models, including zebrafish and mice, we demonstrate a critical role for ZNG1 proteins in regulating cellular Zn homeostasis. Collectively, these data reveal the existence of a family of Zn metallochaperones and assign ZNG1 an important role for intracellular Zn trafficking.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Zinco / Metaloendopeptidases Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Zinco / Metaloendopeptidases Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
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