PMID- 17023543
OWN - NLM
STAT- MEDLINE
DCOM- 20070126
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 103
IP  - 42
DP  - 2006 Oct 17
TI  - Mapping protein dynamics in catalytic intermediates of the redox-driven proton 
      pump cytochrome c oxidase.
PG  - 15398-403
AB  - Redox-driven proton pumps such as cytochrome c oxidase (CcO) are fundamental 
      elements of the energy transduction machinery in biological systems. CcO is an 
      integral membrane protein that acts as the terminal electron acceptor in 
      respiratory chains of aerobic organisms, catalyzing the four-electron reduction 
      of O2 to H2O. This reduction also requires four protons taken from the cytosolic 
      or negative side of the membrane, with an additional uptake of four protons that 
      are pumped across the membrane. Therefore, the proton pump must embody a "gate," 
      which provides alternating access of protons to one or the other side of the 
      membrane but never both sides simultaneously. However, the exact mechanism of 
      proton translocation through CcO remains unknown at the molecular level. 
      Understanding pump function requires knowledge of the nature and location of 
      these structural changes that is often difficult to access with crystallography 
      or NMR spectroscopy. In this paper, we demonstrate, with amide hydrogen/deuterium 
      exchange MS, that transitions between catalytic intermediates in CcO are 
      orchestrated with opening and closing of specific proton pathways, providing an 
      alternating access for protons to the two sides of the membrane. An analysis of 
      these results in the framework of the 3D structure of CcO indicate the spatial 
      location of a gate, which controls the unidirectional proton flux through the 
      enzyme and points to a mechanism by which CcO energetically couples electron 
      transfer to proton translocation.
FAU - Busenlehner, Laura S
AU  - Busenlehner LS
AD  - Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University 
      School of Medicine, Nashville, TN 37232-0146, USA.
FAU - Salomonsson, Lina
AU  - Salomonsson L
FAU - Brzezinski, Peter
AU  - Brzezinski P
FAU - Armstrong, Richard N
AU  - Armstrong RN
LA  - eng
GR  - P30 ES000267/ES/NIEHS NIH HHS/United States
GR  - F32 ES013105/ES/NIEHS NIH HHS/United States
GR  - F32 ES013105-02/ES/NIEHS NIH HHS/United States
GR  - P30 ES00267/ES/NIEHS NIH HHS/United States
GR  - T32 ES007028/ES/NIEHS NIH HHS/United States
GR  - R01 GM030910/GM/NIGMS NIH HHS/United States
GR  - F32 ES013105-01/ES/NIEHS NIH HHS/United States
GR  - T32 ES07028/ES/NIEHS NIH HHS/United States
GR  - R01 GM30910/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061005
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Protein Subunits)
RN  - 0 (Protons)
RN  - 7YNJ3PO35Z (Hydrogen)
RN  - AR09D82C7G (Deuterium)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Biological Transport/physiology
MH  - Deuterium/chemistry/metabolism
MH  - Electron Transport Complex IV/*chemistry/genetics/*metabolism
MH  - Hydrogen/chemistry/metabolism
MH  - Mass Spectrometry
MH  - Oxidation-Reduction
MH  - *Protein Structure, Tertiary
MH  - Protein Subunits/chemistry/genetics/metabolism
MH  - *Protons
MH  - Rhodobacter sphaeroides/metabolism
PMC - PMC1622835
COIS- The authors declare no conflict of interest.
EDAT- 2006/10/07 09:00
MHDA- 2007/01/27 09:00
PMCR- 2007/04/17
CRDT- 2006/10/07 09:00
PHST- 2006/10/07 09:00 [pubmed]
PHST- 2007/01/27 09:00 [medline]
PHST- 2006/10/07 09:00 [entrez]
PHST- 2007/04/17 00:00 [pmc-release]
AID - 0601451103 [pii]
AID - 3666 [pii]
AID - 10.1073/pnas.0601451103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15398-403. doi: 
      10.1073/pnas.0601451103. Epub 2006 Oct 5.