Redox-regulated dynamic interplay between Cox19 and the copper-binding protein Cox11 in the intermembrane space of mitochondria facilitates biogenesis of cytochrome c oxidase.
Members of the twin Cx9C protein family constitute the largest group of proteins in the intermembrane space (IMS) of mitochondria. Despite their conserved nature and their essential role in the biogenesis of the respiratory chain, the molecular function of twin Cx9C proteins is largely unknown. We performed a SILAC-based quantitative proteomic analysis to identify interaction partners of the conserved twin Cx9C protein Cox19. We found that Cox19 interacts in a dynamic manner with Cox11, a copper transfer protein that facilitates metalation of the Cu(B) center of subunit 1 of cytochrome c oxidase. The interaction with Cox11 is critical for the stable accumulation of Cox19 in mitochondria. Cox19 consists of a helical hairpin structure that forms a hydrophobic surface characterized by two highly conserved tyrosine-leucine dipeptides. These residues are essential for Cox19 function and its specific binding to a cysteine-containing sequence in Cox11. Our observations suggest that an oxidative modification of this cysteine residue of Cox11 stimulates Cox19 binding, pointing to a redox-regulated interplay of Cox19 and Cox11 that is critical for copper transfer in the IMS and thus for biogenesis of cytochrome c oxidase.
Cell Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Manuela
M
Bode
Cell Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Michael W
MW
Woellhaf
Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany.
Maria
M
Bohnert
Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
Martin
M
van der Laan
Molecular Biotechnology and Systems Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Frederik
F
Sommer
Medical Biochemistry and Molecular Biology, Saarland University, 66424 Homburg, Germany.
Martin
M
Jung
Medical Biochemistry and Molecular Biology, Saarland University, 66424 Homburg, Germany.
Richard
R
Zimmermann
Molecular Biotechnology and Systems Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Michael
M
Schroda
Cell Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany hannes.herrmann@biologie.uni-kl.de.
Johannes M
JM
Herrmann
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000096:biosynthesis* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary; D040901:Proteomics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
C086106:COX11 protein, S cerevisiae; D002352:Carrier Proteins; C520018:Cox19 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C023548:copper-binding protein; D003576:Electron Transport Complex IV