PMID- 31851937
OWN - NLM
STAT- MEDLINE
DCOM- 20200914
LR  - 20210110
IS  - 2211-1247 (Electronic)
VI  - 29
IP  - 12
DP  - 2019 Dec 17
TI  - COA6 Is Structurally Tuned to Function as a Thiol-Disulfide Oxidoreductase in 
      Copper Delivery to Mitochondrial Cytochrome c Oxidase.
PG  - 4114-4126.e5
LID - S2211-1247(19)31536-0 [pii]
LID - 10.1016/j.celrep.2019.11.054 [doi]
AB  - In eukaryotes, cellular respiration is driven by mitochondrial cytochrome c 
      oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic 
      activity. Insertion of copper into its catalytically active subunits, including 
      COX2, is a complex process that requires metallochaperones and redox proteins 
      including SCO1, SCO2, and COA6, a recently discovered protein whose molecular 
      function is unknown. To uncover the molecular mechanism by which COA6 and SCO 
      proteins mediate copper delivery to COX2, we have solved the solution structure 
      of COA6, which reveals a coiled-coil-helix-coiled-coil-helix domain typical of 
      redox-active proteins found in the mitochondrial inter-membrane space. 
      Accordingly, we demonstrate that COA6 can reduce the copper-coordinating 
      disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. 
      Finally, our determination of the interaction surfaces and reduction potentials 
      of COA6 and its client proteins provides a mechanism of how metallochaperone and 
      disulfide reductase activities are coordinated to deliver copper to CcO.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Soma, Shivatheja
AU  - Soma S
AD  - Department of Biochemistry and Biophysics, MS 3474, Texas A&M University, College 
      Station, TX 77843, USA.
FAU - Morgada, Marcos N
AU  - Morgada MN
AD  - Instituto de Biologia Molecular y Celular de Rosario (IBR-CONICET), Area 
      Biofisica, Departamento de Quimica Biologica, Facultad de Ciencias Bioquimicas y 
      Farmaceuticas, Universidad Nacional de Rosario, Rosario (2000), Argentina.
FAU - Naik, Mandar T
AU  - Naik MT
AD  - Department of Biochemistry and Biophysics, MS 3474, Texas A&M University, College 
      Station, TX 77843, USA.
FAU - Boulet, Aren
AU  - Boulet A
AD  - Department of Biochemistry, Microbiology and Immunology, University of 
      Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
FAU - Roesler, Anna A
AU  - Roesler AA
AD  - Department of Biochemistry, Microbiology and Immunology, University of 
      Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
FAU - Dziuba, Nathaniel
AU  - Dziuba N
AD  - Department of Biochemistry and Biophysics, MS 3474, Texas A&M University, College 
      Station, TX 77843, USA.
FAU - Ghosh, Alok
AU  - Ghosh A
AD  - Department of Biochemistry and Biophysics, MS 3474, Texas A&M University, College 
      Station, TX 77843, USA.
FAU - Yu, Qinhong
AU  - Yu Q
AD  - Department of Chemistry, University of California, Davis, Davis, CA 95616, USA.
FAU - Lindahl, Paul A
AU  - Lindahl PA
AD  - Department of Biochemistry and Biophysics, MS 3474, Texas A&M University, College 
      Station, TX 77843, USA; Department of Chemistry, Texas A&M University, College 
      Station, TX 77843, USA.
FAU - Ames, James B
AU  - Ames JB
AD  - Department of Chemistry, University of California, Davis, Davis, CA 95616, USA.
FAU - Leary, Scot C
AU  - Leary SC
AD  - Department of Biochemistry, Microbiology and Immunology, University of 
      Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
FAU - Vila, Alejandro J
AU  - Vila AJ
AD  - Instituto de Biologia Molecular y Celular de Rosario (IBR-CONICET), Area 
      Biofisica, Departamento de Quimica Biologica, Facultad de Ciencias Bioquimicas y 
      Farmaceuticas, Universidad Nacional de Rosario, Rosario (2000), Argentina.
FAU - Gohil, Vishal M
AU  - Gohil VM
AD  - Department of Biochemistry and Biophysics, MS 3474, Texas A&M University, College 
      Station, TX 77843, USA. Electronic address: vgohil@tamu.edu.
LA  - eng
GR  - R01 EY012347/EY/NEI NIH HHS/United States
GR  - R01 GM111672/GM/NIGMS NIH HHS/United States
GR  - R35 GM127021/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (COA6 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (SCO1 protein, human)
RN  - 0 (SCO2 protein, human)
RN  - EC 1.8.4.2 (Protein Disulfide Reductase (Glutathione))
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Carrier Proteins/genetics/*metabolism
MH  - Electron Transport Complex IV/genetics/*metabolism
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Molecular Chaperones/metabolism
MH  - Mutation/genetics
MH  - Protein Binding
MH  - Protein Disulfide Reductase (Glutathione)/genetics/*metabolism
PMC - PMC6946597
MID - NIHMS1547110
OTO - NOTNLM
OT  - COA6
OT  - COX2
OT  - Mitochondria
OT  - SCO1
OT  - SCO2
OT  - copper
OT  - cytochrome c oxidase
OT  - metallochaperone
OT  - thiol-disulfide oxidoredcutase
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2019/12/19 06:00
MHDA- 2020/09/15 06:00
PMCR- 2020/01/07
CRDT- 2019/12/19 06:00
PHST- 2019/07/03 00:00 [received]
PHST- 2019/10/07 00:00 [revised]
PHST- 2019/11/13 00:00 [accepted]
PHST- 2019/12/19 06:00 [entrez]
PHST- 2019/12/19 06:00 [pubmed]
PHST- 2020/09/15 06:00 [medline]
PHST- 2020/01/07 00:00 [pmc-release]
AID - S2211-1247(19)31536-0 [pii]
AID - 10.1016/j.celrep.2019.11.054 [doi]
PST - ppublish
SO  - Cell Rep. 2019 Dec 17;29(12):4114-4126.e5. doi: 10.1016/j.celrep.2019.11.054.