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    ATP synthase generation of rotation For the synthesis of each ATP, the g-subunit rotates through 120@ 12 c-subunits / ring 10 csubunits in S. Cerevisiae 14 cring in chloroplasts Estimates of H+ / ATP are in the range 3-4 the bioenergetic cost of making an ATP molecule in mammalian mitochondria Watt et al (2010) PNAS 107,

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    ATP synthase generation of rotation For the synthesis of each ATP, the g-subunit rotates through 120@ 12 c-subunits / ring 10 csubunits in S. Cerevisiae 14 cring in chloroplasts Estimates of H+ / ATP are in the range 3-4 the bioenergetic cost of making an ATP molecule in mammalian mitochondria Watt et al (2010) PNAS 107,

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    27 views57 pages

    Classic Paper-2010 For Web - 0

    Uploaded by

    vladaspu
    ATP synthase generation of rotation For the synthesis of each ATP, the g-subunit rotates through 120@ 12 c-subunits / ring 10 csubunits in S. Cerevisiae 14 cring in chloroplasts Estimates of H+ / ATP are in the range 3-4 the bioenergetic cost of making an ATP molecule in mammalian mitochondria Watt et al (2010) PNAS 107,

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    of 57

    Classic papers in biochemistry

    Structure at 2.8 resolution of F1-ATPase from bovine heart mitochondria


    Nature, 370, 1994, 621-628 Abrahams, Leslie, Lutter & Walker

    Thursday, 2 December 2010

    Mitochondria and F-ATPase

    1980-1994

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

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    Thursday, 2 December 2010

    How is pmf coupled to ATP synthesis?


    Direct (Mitchell, Williams) Indirect (Boyer, others)

    Thursday, 2 December 2010

    Thursday, 2 December 2010

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    The thirteen proteins encoded in mitochondrial DNA

    Human mtDNA
    7 proteins 1 protein 2 proteins 3 proteins

    2NAD+ 2NADH
    2 e

    4H
    +

    FADH
    2

    FA D 2 e Q QH
    2

    2H
    +

    4H
    +

    H2 O

    [O ]
    2 e

    ATP ADP + Pi

    3-4 H+

    Q QH
    2

    4H
    +
    Thursday, 2 December 2010

    2 H+ e

    2 e

    3-4 H+ 2H
    +

    Cyt c

    Thursday, 2 December 2010

    P-loop sequences in F1-ATPase

    Thursday, 2 December 2010

    P-loop sequences in F1-ATPase


    consensus 169-1 159-163 G X X X X G KT G D R QT G KT G G A GV G KT

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Paul Boyer

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    ATP binding site of TP

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    The ATP synthase

    Thursday, 2 December 2010

    20 nm

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Generation of rotation

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    The H+/ATP and Na+/ATP ratios

    For the synthesis of each ATP, the -subunit rotates through 120 12 c-subunits/ring



    H+/ATP = 4 H+/ATP = 3.3 H+/ATP = 4.7

    10 c-subunits in S. cerevisiae

    14 c-subunits in chloroplasts

    11 c-subunits in Na+-motive F-ATPases


    Na+/ATP = 3.7 Estimates of H+/ATP are in the range 3-4

    Thursday, 2 December 2010

    The mammalian c-ring


    The bioenergetic cost of making an ATP molecule in mammalian mitochondria

    Watt et al (2010) PNAS 107, 16823

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    P/O ratio in mammalian mitochondria NADH 2e- to O2 =10 H+ pumped out + Succinate 2e to O2 = 6 H pumped out ADP/ATP exchange + Pi/H+ symport = 1 H+ in ATP synthase ATP synthesis H /ATP = 8/3 = 2.7 H+/ATP = 3.7
    +

    Moles ADP phosphorylated/2e to O2 = P/O ratio e donor NADH Succinate


    -

    P/O calc 10/3.7=2.7 6/3.7=1.6

    P/O exp 2.5 1.5

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Thursday, 2 December 2010

    Species known to have trimethyl-lysine-43

    Man, cows, sheep, pigs, rabbit, mice, rats Chickens Flies (Diptera) NB Yeast has K43, but not trimethylated

    Thursday, 2 December 2010

    17

    Lindsay Baker, Mike Runswick, John Walker and John Rubinstein, unpublished work
    Thursday, 2 December 2010

    Lindsay Baker, Mike Runswick, John Walker and John Rubinstein, unpublished work
    Thursday, 2 December 2010

    Unresolved issues

    The a-c-ring interface Understanding differences between F-ATPases (regulation, ring symmetries, peripheral stalks) Reconciling structures and biophysics

    Thursday, 2 December 2010

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