Reference: Zhang Y, et al. (2011) Investigation of in vivo diferric tyrosyl radical formation in Saccharomyces cerevisiae Rnr2 protein: requirement of Rnr4 and contribution of Grx3/4 AND Dre2 proteins. J Biol Chem 286(48):41499-509

Reference Help

Abstract


The ?(2) subunit of class Ia ribonucleotide reductase (RNR) contains a diferric tyrosyl radical cofactor (Fe(2)(III)-Tyr(?)) that is essential for nucleotide reduction. The ?(2) subunit of Saccharomyces cerevisiae is a heterodimer of Rnr2 (?) and Rnr4 (?'). Although only ? is capable of iron binding and Tyr(?) formation, cells lacking ?' are either dead or exhibit extremely low Tyr(?) levels and RNR activity depending on genetic backgrounds. Here, we present evidence supporting the model that ?' is required for iron loading and Tyr(?) formation in ? in vivo via a pathway that is likely dependent on the cytosolic monothiol glutaredoxins Grx3/Grx4 and the Fe-S cluster protein Dre2. rnr4 mutants are defective in iron loading into nascent ? and are hypersensitive to iron depletion and the Tyr(?)-reducing agent hydroxyurea. Transient induction of ?' in a GalRNR4 strain leads to a concomitant increase in iron loading and Tyr(?) levels in ?. Tyr(?) can also be rapidly generated using endogenous iron when permeabilized ?rnr4 spheroplasts are supplemented with recombinant ?' and is inhibited by adding an iron chelator prior to, but not after, ?' supplementation. The growth defects of rnr4 mutants are enhanced by deficiencies in grx3/grx4 and dre2. Moreover, depletion of Dre2 in GalDRE2 cells leads to a decrease in both Tyr(?) levels and ??' activity. This result, in combination with previous findings that a low level of Grx3/4 impairs RNR function, strongly suggests that Grx3/4 and Dre2 serve in the assembly of the deferric Tyr(?) cofactor in RNR.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Zhang Y, Liu L, Wu X, An X, Stubbe J, Huang M
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference