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      • HARVEST
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      Molecular Mechanism of E. coli ATP synthase: Structural Analysis of the Proton Channel

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      PIERSON-DISSERTATION.pdf (38.81Mb)
      Date
      2013-04-25
      Author
      Pierson, Hannah
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
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      Abstract
      Adenosine triphosphate (ATP) is the energy currency of all living cells and its production is a key reaction in the energy metabolism of living organisms. Cells produce most of the ATP they require through ATP synthase, a unique molecular rotary motor driven by the movement of protons across the lipid membrane. In E.coli, ATP synthase is composed of a soluble domain called F1, which houses the catalytic sites, and a transmembrane domain called F0 that shuttles protons across the membrane to drive ATP production in the F1 sector. The F0 domain is built of three subunit types: subunit a and a dimer of subunit b form the stator of the motor, while a decameric c ring forms the rotor. The dynamic interface between a and c10 forms the proton channel. The ultimate goal of this work is to determine the structure of the proton transport machinery and understand the molecular mechanism of proton translocation in ATP synthase. We have characterized some of the key events in the stepwise assembly of the F0--complex. We have designed and validated a model protein, consisting of genetically fused subunits a and c, for structural studies. We have made progress towards determining the structure of the proton channel, including the development of a novel procedure for purification of subunit a and the a/c fusion protein, and crystallization of subunit a. Medical applications of this work include the potential development of novel antibiotic compounds, as well as the characterization and potential treatment of three human diseases caused by disruptions in proton transport through F0.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Biochemistry
      Program
      Biochemistry
      Supervisor
      Dmitriev, Oleg Y.
      Committee
      Lee, Jeremy; Howard, Peter S.; Moore, Stanley; Pato, Mary; Wilkens, Stephan
      Copyright Date
      April 2013
      URI
      http://hdl.handle.net/10388/ETD-2013-04-996
      Subject
      ATP synthase
      subunit a
      membrane protein
      structure studies
      NMR
      X-ray crystallography
      proton channel
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