Life science
Medicine, Structure-based drug design, Energy-efficient nanodevice

CryoEM structures of bacterial flagellar motor useful for de主要図表：図１、図２
signing anti-bacterial drugs and rotary nanodevices
Graduate School of Frontier Biosciences, JEOL YOKOGUSHI Research Alliance Laboratories
SA Professor Keiichi Namba

主要図表：図１、図２

Researchmap https://researchmap.jp/read0096830

Life science

Abstract

主要図表：図１、図２

The recent progress in electron cryomicroscopy (cryoEM) andsingle particle image analysis has made it possible for the structure
determination of biological macromolecules to be carried out froma small amount of solution sample as mall as a few μg. Now thedata collection throughput is as high as 30,000 cryoEM images per
day so that collection of a few thousands cryoEM images needed
for structural analysis can be completed within a few hours. The
structure-based drug screening that pharmaceutical companies
are keen to carry out can be done very efficiently. We utilized thistechnology to determine the structures of multiple rings of the bacterial flagellar motor, and they revealed the mechanisms of torquetransmission by the rotor ring and nearly zero friction of bushing forenergy-efficient high-speed rotation of the motor.

Fig. 1 Entire structure of the bacterial flagellar basal body spanning the inner andouter membranes as a nanoscale rotary motor (left) and high-resolution density
map of the rotor S ring (right).

▍ Background & Results
Because the mechanisms of life in the living organisms are driven by dynamic networks of biological macromolecules based on
3D structures, the structural information is essential for our mechanistic understanding of life. Many bacteria, such as Salmonella,
have a motile organelle called the flagellum, composed of a longhelical filament as a propeller and a rotary motor, to swim aroundto find favorable environments for their survival. The structure ofFig. 2 High-resolution structures of the bacterial flagellar basal body (left) and its
the rotary motor had been elusive, and the mechanisms of torquebushing LP ring (right).
generation-transmission and friction-less high-speed rotation of thedrive shaft inside the bushing remained unknown.
By the recent progress in cryoEM with automated high-throughput data collection, it is now possible for structural analysis toreach atomic resolution within a relatively short period of time. This
allowed the structure of the flagellar motor to be determined atnear atomic resolution. The structure of the rotor ring called the MS
ring has shown that it is composed of 34 subunits of FliF protein in
two different conformations, generating a complex structure made１2.11ご⾃⾝の顔写真のご提供
of disks and cylinder with three different, 34-fold, 23-fold, and１2.
ご⾃⾝の顔写真のご提供
fold rotational symmetries. The bushing called the LP ring is made※ 印刷可能な解像度のものを電⼦ファイルにてご提供ください。
※ 印刷可能な解像度のものを電⼦ファイルにてご提供ください。
of 26 subunits of FliH and FliI, forming an intricate network of longanti-parallel β-strands to build the solid wall of the hollow cylinder
as a bushing. The inner surface of the LP ring is charged bothFig. 3 Electrostatic potential distributions on the surfaces of the drive shaft (left)
positively and negatively and closely faces the negatively charged
and the bushing LP ring (right).
outer surface of the drive shaft to realize nearly zero friction forenergy-efficient high-speed rotation of the motor by well-balanced
electrostatic forces.

▍１2. ご⾃⾝の顔写真のご提供

Significance of the research and Future perspective※ 印刷可能な解像度のものを電⼦ファイルにてご提供ください。

The structural information of the bacterial flagellar motor at atomic level will be useful for future engineering applications, such asa design principle of highly energy efficient self-assembling nanodevices, as well as the basis for the development of anti-bacterialdrugs.

P a t e n t
Kawamoto, Akihiro; Miyata, Tomoko; Makino, Fumiaki et al. Native flagellar MS ring is formed by 34 subunits with 23-fold and 11-fold subsymmetries.
Nature Communications. 2021; 12: 4223. doi: 10.1038/s41467-021-24507-9.
Yamaguchi, Tomoko; Makino, Fumiaki; Miyata, Tomoko et al. Structure of the molecular bushing of the bacterial flagellar motor. Nature Communications.
2021; 12: 4456. doi: 10.1038/s41467-021-24715-3.
https://www.fbs.osaka-u.ac.jp/en/research_results/papers/detail/1026
URL
https://www.fbs.osaka-u.ac.jp/en/research_results/papers/detail/1028
K e y w o r d electron cryomicroscopy, single particle image analysis, structural analysis of biological macromolecules, protein nanomachine, bacterial flagellar motor
Tr e a t i s e以