The characterization and role of zinc binding in yeast Cox4

H. Jerome Coyne, Simone Ciofi-Baffoni, Lucia Banci, Ivano Bertini, Limei Zhang, Graham N. George, Dennis R. Winge

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in nonfunctional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two β sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

Original languageEnglish (US)
Pages (from-to)8926-8934
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number12
DOIs
StatePublished - Mar 23 2007

Fingerprint

Electron Transport Complex IV
Yeast
Zinc
Yeasts
Ligands
Facings
Fungal Proteins
Mitochondrial Membranes
Cysteine
Conformations
Catalytic Domain
Proteins
Substitution reactions
Nuclear magnetic resonance
X-Rays
Ions
Membranes
X rays
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Coyne, H. J., Ciofi-Baffoni, S., Banci, L., Bertini, I., Zhang, L., George, G. N., & Winge, D. R. (2007). The characterization and role of zinc binding in yeast Cox4. Journal of Biological Chemistry, 282(12), 8926-8934. https://doi.org/10.1074/jbc.M610303200

The characterization and role of zinc binding in yeast Cox4. / Coyne, H. Jerome; Ciofi-Baffoni, Simone; Banci, Lucia; Bertini, Ivano; Zhang, Limei; George, Graham N.; Winge, Dennis R.

In: Journal of Biological Chemistry, Vol. 282, No. 12, 23.03.2007, p. 8926-8934.

Research output: Contribution to journalArticle

Coyne, HJ, Ciofi-Baffoni, S, Banci, L, Bertini, I, Zhang, L, George, GN & Winge, DR 2007, 'The characterization and role of zinc binding in yeast Cox4', Journal of Biological Chemistry, vol. 282, no. 12, pp. 8926-8934. https://doi.org/10.1074/jbc.M610303200
Coyne HJ, Ciofi-Baffoni S, Banci L, Bertini I, Zhang L, George GN et al. The characterization and role of zinc binding in yeast Cox4. Journal of Biological Chemistry. 2007 Mar 23;282(12):8926-8934. https://doi.org/10.1074/jbc.M610303200
Coyne, H. Jerome ; Ciofi-Baffoni, Simone ; Banci, Lucia ; Bertini, Ivano ; Zhang, Limei ; George, Graham N. ; Winge, Dennis R. / The characterization and role of zinc binding in yeast Cox4. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 12. pp. 8926-8934.
@article{81c83f25931048869a9b283c801cbc22,
title = "The characterization and role of zinc binding in yeast Cox4",
abstract = "Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in nonfunctional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two β sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.",
author = "Coyne, {H. Jerome} and Simone Ciofi-Baffoni and Lucia Banci and Ivano Bertini and Limei Zhang and George, {Graham N.} and Winge, {Dennis R.}",
year = "2007",
month = "3",
day = "23",
doi = "10.1074/jbc.M610303200",
language = "English (US)",
volume = "282",
pages = "8926--8934",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - The characterization and role of zinc binding in yeast Cox4

AU - Coyne, H. Jerome

AU - Ciofi-Baffoni, Simone

AU - Banci, Lucia

AU - Bertini, Ivano

AU - Zhang, Limei

AU - George, Graham N.

AU - Winge, Dennis R.

PY - 2007/3/23

Y1 - 2007/3/23

N2 - Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in nonfunctional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two β sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

AB - Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in nonfunctional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two β sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

UR - http://www.scopus.com/inward/record.url?scp=34247898912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247898912&partnerID=8YFLogxK

U2 - 10.1074/jbc.M610303200

DO - 10.1074/jbc.M610303200

M3 - Article

VL - 282

SP - 8926

EP - 8934

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -