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A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery.
Frey, Avery G; Palenchar, Daniel J; Wildemann, Justin D; Philpott, Caroline C.
Afiliação
  • Frey AG; From the Genetics and Metabolism Section, Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 and.
  • Palenchar DJ; From the Genetics and Metabolism Section, Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 and.
  • Wildemann JD; the College of Medicine, Ohio State University, Columbus, Ohio 43210.
  • Philpott CC; From the Genetics and Metabolism Section, Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 and Carolinep@mail.nih.gov.
J Biol Chem ; 291(43): 22344-22356, 2016 10 21.
Article em En | MEDLINE | ID: mdl-27519415
Cells contain hundreds of proteins that require iron cofactors for activity. Iron cofactors are synthesized in the cell, but the pathways involved in distributing heme, iron-sulfur clusters, and ferrous/ferric ions to apoproteins remain incompletely defined. In particular, cytosolic monothiol glutaredoxins and BolA-like proteins have been identified as [2Fe-2S]-coordinating complexes in vitro and iron-regulatory proteins in fungi, but it is not clear how these proteins function in mammalian systems or how this complex might affect Fe-S proteins or the cytosolic Fe-S assembly machinery. To explore these questions, we use quantitative immunoprecipitation and live cell proximity-dependent biotinylation to monitor interactions between Glrx3, BolA2, and components of the cytosolic iron-sulfur cluster assembly system. We characterize cytosolic Glrx3·BolA2 as a [2Fe-2S] chaperone complex in human cells. Unlike complexes formed by fungal orthologs, human Glrx3-BolA2 interaction required the coordination of Fe-S clusters, whereas Glrx3 homodimer formation did not. Cellular Glrx3·BolA2 complexes increased 6-8-fold in response to increasing iron, forming a rapidly expandable pool of Fe-S clusters. Fe-S coordination by Glrx3·BolA2 did not depend on Ciapin1 or Ciao1, proteins that bind Glrx3 and are involved in cytosolic Fe-S cluster assembly and distribution. Instead, Glrx3 and BolA2 bound and facilitated Fe-S incorporation into Ciapin1, a [2Fe-2S] protein functioning early in the cytosolic Fe-S assembly pathway. Thus, Glrx3·BolA is a [2Fe-2S] chaperone complex capable of transferring [2Fe-2S] clusters to apoproteins in human cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas / Proteínas de Transporte / Citosol / Proteínas Ferro-Enxofre Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas / Proteínas de Transporte / Citosol / Proteínas Ferro-Enxofre Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article