Chapter 4
Concluding Remarks
Abstract AcrB, a homotrimer possessing a triangular-prism shape, is the principal
part of the AcrA–AcrB–TolC complex which extrudes a variety of drugs from a cell.
AcrB comprises three protomers which are in access (A), binding (B), and extrusion
(E) states along a drug-transport cycle, respectively. According to a suggestion made
in the literature, the three protomers exhibit a sequential conformational change
expressed as (A, B, E)→(B, E, A)→(E, A, B)→(A, B, E). This change, which is
referred to as the “functional rotation”, is achieved with the use of the so-called
proton motive force yielding repeated proton binding to and dissociation from AcrB.
In this chapter, we point out that F 1 -ATPase considered in Chap. 3 and AcrB share
physically the same rotation mechanism. Whenever the structure of one of the three
portions forming a protein complex is perturbed in the direction that a solvent-entropy
loss is caused, the structures of the other two portions are reorganized to make up
for the loss. We also comment on the rotation mechanism of V 1 -ATPase which we
intend to explore in the next stage.
Keywords AcrB · Proton motive force · Drug extrusion · Multidrug efflux ·
Functional rotation · V 1 -ATPase
4.1 Functional Rotation of AcrB
In Chap. 3, we have discussed the functional expression of F 1 -ATPase, the unidirectional rotation of the γ subunit. The important points can be summarized as follows:
The system of interest comprises not only F 1 -ATPase but also water in which
ATP, ADP, and Pi are dissolved (water is not the external system for F 1 -ATPase);
F 1 -ATPase is coupled with the ATP hydrolysis reaction, an irreversible process
accompanied by a decrease in system free energy; F 1 -ATPase is thus involved in
the ATP hydrolysis cycle (i.e., the ATP binding to F 1 -ATPase, ATP hydrolysis,
and dissociation of ADP and Pi from F 1 -ATPase) which spontaneously occurs; the
system performs essentially no mechanical work during the rotation; and the force
rotating the γ subunit is generated by not ATP but water. The force originates from
the translational displacement of water molecules in the whole system.
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021
M. Kinoshita, Mechanism of Functional Expression of F 1 -ATPase,
SpringerBriefs in Molecular Science,
https://doi.org/10.1007/978-981-33-6232-1_4
63
Concluding Remarks
Abstract AcrB, a homotrimer possessing a triangular-prism shape, is the principal
part of the AcrA–AcrB–TolC complex which extrudes a variety of drugs from a cell.
AcrB comprises three protomers which are in access (A), binding (B), and extrusion
(E) states along a drug-transport cycle, respectively. According to a suggestion made
in the literature, the three protomers exhibit a sequential conformational change
expressed as (A, B, E)→(B, E, A)→(E, A, B)→(A, B, E). This change, which is
referred to as the “functional rotation”, is achieved with the use of the so-called
proton motive force yielding repeated proton binding to and dissociation from AcrB.
In this chapter, we point out that F 1 -ATPase considered in Chap. 3 and AcrB share
physically the same rotation mechanism. Whenever the structure of one of the three
portions forming a protein complex is perturbed in the direction that a solvent-entropy
loss is caused, the structures of the other two portions are reorganized to make up
for the loss. We also comment on the rotation mechanism of V 1 -ATPase which we
intend to explore in the next stage.
Keywords AcrB · Proton motive force · Drug extrusion · Multidrug efflux ·
Functional rotation · V 1 -ATPase
4.1 Functional Rotation of AcrB
In Chap. 3, we have discussed the functional expression of F 1 -ATPase, the unidirectional rotation of the γ subunit. The important points can be summarized as follows:
The system of interest comprises not only F 1 -ATPase but also water in which
ATP, ADP, and Pi are dissolved (water is not the external system for F 1 -ATPase);
F 1 -ATPase is coupled with the ATP hydrolysis reaction, an irreversible process
accompanied by a decrease in system free energy; F 1 -ATPase is thus involved in
the ATP hydrolysis cycle (i.e., the ATP binding to F 1 -ATPase, ATP hydrolysis,
and dissociation of ADP and Pi from F 1 -ATPase) which spontaneously occurs; the
system performs essentially no mechanical work during the rotation; and the force
rotating the γ subunit is generated by not ATP but water. The force originates from
the translational displacement of water molecules in the whole system.
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021
M. Kinoshita, Mechanism of Functional Expression of F 1 -ATPase,
SpringerBriefs in Molecular Science,
https://doi.org/10.1007/978-981-33-6232-1_4
63