JBIC Journal of Biological Inorganic Chemistry

, Volume 11, Issue 4, pp 459–466

Crystal structure of yeast Sco1

Authors

  • Carnie Abajian
    • Department of Biochemistry, Molecular Biology, and Cell BiologyNorthwestern University
    • Department of ChemistryNorthwestern University
    • Department of Biochemistry, Molecular Biology, and Cell BiologyNorthwestern University
    • Department of ChemistryNorthwestern University
Original Paper

DOI: 10.1007/s00775-006-0096-7

Cite this article as:
Abajian, C. & Rosenzweig, A.C. J Biol Inorg Chem (2006) 11: 459. doi:10.1007/s00775-006-0096-7

Abstract

The Sco family of proteins are involved in the assembly of the dinuclear CuA site in cytochrome c oxidase (COX), the terminal enzyme in aerobic respiration. These proteins, which are found in both eukaryotes and prokaryotes, are characterized by a conserved CXXXC sequence motif that binds copper ions and that has also been proposed to perform a thiol:disulfide oxidoreductase function. The crystal structures of Saccharomyces cerevisiae apo Sco1 (apo-ySco1) and Sco1 in the presence of copper ions (Cu–ySco1) were determined to 1.8- and 2.3-Å resolutions, respectively. Yeast Sco1 exhibits a thioredoxin-like fold, similar to that observed for human Sco1 and a homolog from Bacillus subtilis. The Cu–ySco1 structure, obtained by soaking apo-ySco1 crystals in copper ions, reveals an unexpected copper-binding site involving Cys181 and Cys216, cysteine residues present in ySco1 but not in other homologs. The conserved CXXXC cysteines, Cys148 and Cys152, can undergo redox chemistry in the crystal. An essential histidine residue, His239, is located on a highly flexible loop, denoted the Sco loop, and can adopt positions proximal to both pairs of cysteines. Interactions between ySco1 and its partner proteins yeast Cox17 and yeast COX2 are likely to occur via complementary electrostatic surfaces. This high-resolution model of a eukaryotic Sco protein provides new insight into Sco copper binding and function.

Keywords

Cytochrome c oxidaseSco1Cox17Copper chaperoneCrystal structure

Abbreviations

apo-ySco1

Apo form of ySco1 truncate

BsSco

Soluble truncate of Bacillus subtilis Sco

COX

Cytochrome c oxidase

COX1

Subunit I of cytochrome c oxidase

COX2

Subunit II of cytochrome c oxidase

COX3

Subunit III of cytochrome c oxidase

Cu–ySco1

Copper(I)-soaked form of ySco1 truncate

hSco1

Soluble truncate of human Sco1

hSco2

Soluble truncate of human Sco2

IM

Mitochondrial inner membrane

IMS

Mitochondrial intermembrane space

rmsd

Root mean square deviation

TCEP

Tris(2-carboxylethyl)phosphine

Tris

Tris(hydroxymethyl)aminomethane

yCox17

Saccharomyces cerevisiae Cox17

ySco1

Saccharomyces cerevisiae Sco1 soluble truncate lacking the N-terminal 95 residues

Copyright information

© SBIC 2006