Molecular mechanism for rotational switching of the bacterial flagellar motor
The bacterial flagellar motor can rotate in counterclockwise (CCW) or clockwise (CW) senses, and transitions are controlled by the phosphorylated form of the response regulator CheY (CheY-P). To dissect the mechanism underlying flagellar rotational switching, we use Borrelia burgdorferias a model system to determine high-resolution in situ motor structures in cheXand cheY3 mutants, in which motors are locked in either CCW or CW rotation. The structures showed that CheY3-P interacts directly with a switch protein, FliM, inducing a major remodeling of another switch protein, FliG2, and altering its interaction with the torque generator. Our findings lead to a model in which the torque generator rotates in response to an inward flow of H+driven by the proton motive force, and conformational changes in FliG2 driven by CheY3-P allow the switch complex to interact with opposite sides of the rotating torque generator, facilitating rotational switching.
Global Lyme Alliance states the following about the study: https://globallymealliance.org/news/yale-scientists-unlock-new-insight-into-the-lyme-disease-bacterium/
SCIENTISTS AT YALE HAVE UNLOCKED A 50-YEAR PUZZLE OF HOW THE LYME BACTERIUM SPREADS HARMFUL DISEASE.
Published this week in Nature Structural & Molecular Biology, scholars from the Yale Microbial Sciences Institute provide a major new insight to the corkscrew-shaped bacterium – or spirochete – that causes Lyme disease.
The Lyme disease bacterium, Borrelia burgdorferi, spreads through our bodies using a corkscrew-like motion.
For the first time, cryo-electron microscopes have given an up-close look at how the bacterial motors drive clockwise or counter-clockwise motion.
Spirochetes are like smart cars – burrowing into tissues, nerves and joints able to move forward and in reverse. So far scientists have been unable to dissect this mechanism at a molecular level, until now.
“We were able to reveal the direct interactions between a signaling protein and the switch proteins that control the rotational switching in the Lyme disease spirochete for the first time through the lens of a cryo-electron microscope (cryo-EM),” explained the study’s first author, Yunjie Chang, a postdoc in the lab of Jun Liu at Yale University’s West Campus.
The cryo-EM technique flash-freezes the cells to around -270°F then bombards them with electrons to produce thousands of 2D images, which are then combined together to reveal a 3D model, the structural basis to understand the rotational switching.
“This microscope is key,” said senior author Jun Liu, associate professor of Microbial Pathogenesis. “The power allows us to see through the Lyme disease vehicle, to understand how it navigates and disseminates in its hosts, and how in the future we can control it.”