68
4 Concluding Remarks
a structural change of the vessel [12–15]. AcrA/AcrB/TolC is capable of handling
drugs with diverse properties and therefore characterized by the “multidrug efflux”.
This characteristic is conferred upon the vessel only when the solvent-entropy effect
dominates [11, 12, 15].
4.2 Toward Investigation of Unidirectional Rotation
of Central Shaft in V 1 -ATPase
Water-soluble V 1 -ATPase, the catalytic domain of Vacuolar ATPase, is an ATPdriven molecular motor which appears to be quite similar to F 1 -ATPase [17–22].
V 1 -ATPase utilizes the ATP hydrolysis cycle. It comprises A, B, D, and F subunits,
and three AB pairs are hexagonally arranged around the DF subcomplex. The A
and B subunits and the DF subcomplex in V 1 -ATPase correspond to the β, α, and
γ subunits in F 1 -ATPase, respectively. Under the solution condition that the ATP
hydrolysis reaction occurs, V 1 -ATPase hydrolyzes ATP into ADP and Pi, which is
accompanied by the rotation of the DF subcomplex in the counterclockwise direction. V 1 -ATPase has been investigated mostly by Murata and coworkers [17–22],
and several differences between V 1 -ATPase and F 1 -ATPase in the structural characteristics and in the rotational mode have been pointed out. The mechanism of the
functional expression of V 1 -ATPase remains quite elusive. We intend to collaborate
with the group of Murata for clarifying similarities and differences between F 1 -
ATPase and V 1 -ATPase in the packing structure, chemical compounds bound to the
three β or A subunits, and rotational mechanism. Despite the possible differences,
it is definite that the water-entropy effect plays a pivotal role for V 1 -ATPase as well
and the rotational mechanisms of F 1 -ATPase and V 1 -ATPase share the same physical
essence. For V 1 -ATPase, the crystal structures in significantly more different states
have been solved by experiments. The collaboration mentioned above is expected to
not only unveil the rotational mechanism of V 1 -ATPase but also make some of the
arguments for F 1 -ATPase described in Chap. 3 even more convincing or, if necessary,
modify the details of its rotational mechanism.
References
1. Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C (2000) Nature 405:914
2. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A (2006) Nature 443:173
3. Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM (2006) Science 313:1295
4. Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grütter M (2007) PLOS Biol. 5:e7(0106)
5. Yamane T, Murakami S, Ikeguchi M (2013) Biochemistry 52:7648
6. Yasuda S, Kajiwara Y, Takamuku Y, Suzuki N, Murata T, Kinoshita M (2016) J Phys Chem B
120:3833
7. Yasuda S, Kajiwara Y, Toyoda Y, Morimoto K, Suno R, Iwata S, Kobayashi T, Murata T,
Kinoshita M (2017) J Phys Chem B 121:6341
4 Concluding Remarks
a structural change of the vessel [12–15]. AcrA/AcrB/TolC is capable of handling
drugs with diverse properties and therefore characterized by the “multidrug efflux”.
This characteristic is conferred upon the vessel only when the solvent-entropy effect
dominates [11, 12, 15].
4.2 Toward Investigation of Unidirectional Rotation
of Central Shaft in V 1 -ATPase
Water-soluble V 1 -ATPase, the catalytic domain of Vacuolar ATPase, is an ATPdriven molecular motor which appears to be quite similar to F 1 -ATPase [17–22].
V 1 -ATPase utilizes the ATP hydrolysis cycle. It comprises A, B, D, and F subunits,
and three AB pairs are hexagonally arranged around the DF subcomplex. The A
and B subunits and the DF subcomplex in V 1 -ATPase correspond to the β, α, and
γ subunits in F 1 -ATPase, respectively. Under the solution condition that the ATP
hydrolysis reaction occurs, V 1 -ATPase hydrolyzes ATP into ADP and Pi, which is
accompanied by the rotation of the DF subcomplex in the counterclockwise direction. V 1 -ATPase has been investigated mostly by Murata and coworkers [17–22],
and several differences between V 1 -ATPase and F 1 -ATPase in the structural characteristics and in the rotational mode have been pointed out. The mechanism of the
functional expression of V 1 -ATPase remains quite elusive. We intend to collaborate
with the group of Murata for clarifying similarities and differences between F 1 -
ATPase and V 1 -ATPase in the packing structure, chemical compounds bound to the
three β or A subunits, and rotational mechanism. Despite the possible differences,
it is definite that the water-entropy effect plays a pivotal role for V 1 -ATPase as well
and the rotational mechanisms of F 1 -ATPase and V 1 -ATPase share the same physical
essence. For V 1 -ATPase, the crystal structures in significantly more different states
have been solved by experiments. The collaboration mentioned above is expected to
not only unveil the rotational mechanism of V 1 -ATPase but also make some of the
arguments for F 1 -ATPase described in Chap. 3 even more convincing or, if necessary,
modify the details of its rotational mechanism.
References
1. Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C (2000) Nature 405:914
2. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A (2006) Nature 443:173
3. Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM (2006) Science 313:1295
4. Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grütter M (2007) PLOS Biol. 5:e7(0106)
5. Yamane T, Murakami S, Ikeguchi M (2013) Biochemistry 52:7648
6. Yasuda S, Kajiwara Y, Takamuku Y, Suzuki N, Murata T, Kinoshita M (2016) J Phys Chem B
120:3833
7. Yasuda S, Kajiwara Y, Toyoda Y, Morimoto K, Suno R, Iwata S, Kobayashi T, Murata T,
Kinoshita M (2017) J Phys Chem B 121:6341