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we are looking at the turning gamma
subunit and the epsilon subunits and
there's the C ring in the membrane the
f1 complex is outside of the membrane
while the f0 complex is embedded in the
membrane
there's the stalk including the Delta
and the B subunits the alpha subunits
are shown in light pink the beta
subunits are magenta in the middle the
central stalk is rotating the b subunit
stabilizes the hexamer which means that
the hexamer can't rotate we will now
look at a rendering of known structural
states and the conformational changes
that are happening the beta subunits are
seen as a ribbon diagram the ADP and
inorganic phosphate diffuse into the
active site and the ATP has just been
released and simultaneously the
conformational change occurs in the beta
subunit if we zoom into the active site
we can see the molecular structure of
the substrates and the chemical reaction
here is ADP with its two phosphates they
are all held in place by a network of
hydrogen bonds mediated by the amino
acids in the folded structure of the
beta subunits hydrogen bonds stabilized
the base and the sugar but really
primarily the base there's also a
magnesium ion that plays a critical role
in not just stabilizing but also
neutralizing the charge of the
phosphates notice the conformational
changes that are happening when the
inorganic phosphate comes in there is
the promotion of a planar transition
state synthesis of a new phosphodiester
bond is catalyzed and then the subunit
switches to the open conformation upon
this reconfiguration in the beta
subunits ATP is ejected from the active
site the enzyme then resets and restarts
the synthesis of another ATP molecule
this is a summary of the events at the
active site it is also intriguing just
how the C ring rotates we can start with
the analogy of a waterwheel we can
easily grasp the idea
of how a water wheel rotates it's driven
by the flow of water allowing the wooden
fins to go in a particular direction
thus the rotation happens in a specific
direction if the water was to flow in
the opposite direction you would see
rotation of the water wheel in the
opposite direction here we see the sea
ring and the a subunit we don't know the
full structure of the a subunits but we
know that there's an access channel for
protons on the a subunit right in the
intermembrane space and there's a
separate egress channel for protons on
the matrix side in this animation you
see protons flowing out from an
interface between the C ring and the a
subunits but what drives the specific
direction of this rotation for example
if we were looking down it is always a
counterclockwise rotation why and what
drives that on each of the C subunits
within the C ring there is a proton
binding site notice the high
concentration of protons on the
intermembrane side and their flow to the
lower concentration on the matrix side
protons load from the highly
concentrated intermembrane side onto the
c subunits and they are released on the
matrix side where the concentration of
the protons is low but why can't protons
go around the other way as well in
principle just as in the water wheel
analogy the C ring should be able to
rotate in either direction shouldn't it
there are two interconnected reasons for
this unidirectional movement the amino
acid side chains and C subunits would
repel the bound proton so that when a
proton loads from the intermembrane side
the C ring cannot rotate back in the
opposite direction because it is
energetically unfavorable rotating
counterclockwise on the other hand is
energetically favorable because there
are no repulsive interactions remember
there's a concentration gradient that
favors binding of protons on the
intermembrane side and the release of
protons on the matrix side so in summary
the proton gradient determines the
direction of the rotation favoring
movement in the counterclockwise
direction of
searing this avoids unfavorable
interactions with the amino acid side
chains of the searing
you
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