A Single-Amino-Acid Lid Renders a Gas-Tight Compartment within a Membrane-Bound Transporter

Proteins undergo structural fluctuations between nearly isoenergetic substates. Such fluctuations are often intimately linked with the functional properties of proteins. However, in some cases, such as in transmembrane ion transporters, the control of the ion transport requires that the protein is d...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-08, Vol.101 (32), p.11617-11621
Main Authors: Salomonsson, Lina, Lee, Alex, Gennis, Robert B., Brzezinski, Peter, Rees, Douglas C.
Format: Article
Language:English
Subjects:
Active sites
Amino Acids
Binding Sites
Biochemistry
Biological Sciences
Biophysics
Cytochromes
Electron Transport Complex IV - chemistry
Electron Transport Complex IV - metabolism
Enzymes
Gases
Hydrogen - metabolism
Ions
Kinetics
Ligands
Membrane Transport Proteins - chemistry
Membrane Transport Proteins - metabolism
Membranes
Molecules
Motion
Oxygen - metabolism
Protein Conformation
Proteins
Proton Pumps
Protons
Rhodobacter sphaeroides - enzymology
Water channels
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Summary:Proteins undergo structural fluctuations between nearly isoenergetic substates. Such fluctuations are often intimately linked with the functional properties of proteins. However, in some cases, such as in transmembrane ion transporters, the control of the ion transport requires that the protein is designed to restrict the motions in specific regions. In this study, we have investigated the dynamics of a membrane-bound respiratory oxidase, which acts both as an enzyme catalyzing reduction of O2to H2O and as a transmembrane proton pump. The segment of the protein where proton translocation is controlled ("gating" region) overlaps with a channel through which O2is delivered to the catalytic site. We show that the replacement of an amino acid residue with a small side chain (Gly) by one with a larger side chain (Val), in a narrow part of this channel, completely blocks the O2access to the catalytic site and results in formation of a compartment around the site that is impermeable to small gas molecules. Thus, the protein motions cannot counter the blockage introduced by the mutation. These results indicate that the protein motions are restricted in the proton-gating region and that rapid O2delivery to the catalytic site requires a gas channel, which is confined within a rigid protein body.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0402242101