GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20624914

From GONUTS
Jump to: navigation, search
Citation

Bestwick, M, Jeong, MY, Khalimonchuk, O, Kim, H and Winge, DR (2010) Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family. Mol. Cell. Biol. 30:4480-91

Abstract

Three missense SURF1 mutations identified in patients with Leigh syndrome (LS) were evaluated in the yeast homolog Shy1 protein. Introduction of two of the Leigh mutations, F(249)T and Y(344)D, in Shy1 failed to significantly attenuate the function of Shy1 in cytochrome c oxidase (CcO) biogenesis as seen with the human mutations. In contrast, a G(137)E substitution in Shy1 results in a nonfunctional protein conferring a CcO deficiency. The G(137)E Shy1 mutant phenocopied shy1Delta cells in impaired Cox1 hemylation and low mitochondrial copper. A genetic screen for allele-specific suppressors of the G(137)E Shy1 mutant revealed Coa2, Cox10, and a novel factor designated Coa4. Coa2 and Cox10 are previously characterized CcO assembly factors. Coa4 is a twin CX(9)C motif mitochondrial protein localized in the intermembrane space and associated with the inner membrane. Cells lacking Coa4 are depressed in CcO activity but show no impairment in Cox1 maturation or formation of the Shy1-stabilized Cox1 assembly intermediate. To glean insights into the functional role of Coa4 in CcO biogenesis, an unbiased suppressor screen of coa4Delta cells was conducted. Respiratory function of coa4Delta cells was restored by the overexpression of CYC1 encoding cytochrome c. Cyc1 is known to be important at an ill-defined step in the assembly and/or stability of CcO. This new link to Coa4 may begin to further elucidate the role of Cyc1 in CcO biogenesis.

Links

PubMed PMC2937524 Online version:10.1128/MCB.00228-10

Keywords

Amino Acid Sequence; Animals; Cell Respiration/physiology; Electron Transport Complex IV/genetics; Electron Transport Complex IV/metabolism; Humans; Leigh Disease/genetics; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Molecular Sequence Data; Mutation, Missense; Protein Biosynthesis; Protein Subunits/genetics; Protein Subunits/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Sequence Alignment

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:COA4

involved_in

GO:0033617: mitochondrial cytochrome c oxidase assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:COA4

involved_in

GO:0033617: mitochondrial cytochrome c oxidase assembly

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000003344
SGD:S000003809

P

Seeded From UniProt

complete

YEAST:COA4

located_in

GO:0005758: mitochondrial intermembrane space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.