Biology subjects

Motaleb, M. A.

Publications and source records attributed to Motaleb, M. A..

4 recordsLinked to original sources

bioRxiv2026

FlcE latches onto the FliL-stator complex to turbocharge flagellar motility in Borrelia burgdorferi

Periplasmic flagella are essential for the distinctive morphology and motility of the Lyme disease spirochete Borrelia burgdorferi, and motility plays a critical role in its pathogenic lifestyle. These flagella are powered by specialized motors that contain a large spirochete-specific multiprotein collar complex, yet the molecular architecture and mechanisms underlying high-torque motility remain poorly understood. Here, we identify the tetratricopeptide repeat (TPR)-containing protein BB0298 as a previously unrecognized flagellar collar component and rename it FlcE. Loss of flcE results in altered morphology and nearly abolishes the spirochetes motility. Using cryo-electron tomography and biochemical analyses, we show that FlcE occupies a unique position within the collar where it surrounds the FliL-stator complex by binding to FliL and the collar protein FlcA. These findings support a model in which FlcE functions as a molecular "latch" that secures stator assemblies to sustain efficient torque generation. Notably, flcE is conserved across most motile members of the Spirochaetales and is located within the division and cell-wall (dcw) gene cluster. More broadly, the conservation of TPR-containing structural proteins across diverse bacterial flagellar systems suggests a general architectural principle whereby dedicated scaffolds reinforce stator complexes to maximize motor performance under high mechanical loads. ImportanceSpirochetal motility requires the stable engagement of torque-generating stator units, yet the mechanisms that secure these complexes have remained unknown. Here, we identify FlcE as a previously unrecognized collar protein that functions as a molecular latch by restraining the FliL-stator complex. Loss of FlcE destabilizes FliL-stator assemblies and severely impairs motility, demonstrating that peripheral scaffolding is essential for sustaining high torque output in the Lyme disease spirochete Borrelia burgdorferi. The conservation of tetratricopeptide repeat domains in FlcE and other bacterial flagellar proteins further suggests a broader mechanism in which specialized scaffolds anchor and stabilize stator complexes, enabling high torque generation. Because motility is a central virulence determinant in many pathogenic bacteria--including B. burgdorferi during transmission from the tick to the mammalian host and subsequent infection--defining the mechanistic role of FlcE provides important insight into the molecular basis of motility-driven pathogenesis and suggests new strategies for disrupting bacterial infection.

microbiology↗

bioRxiv2020

Molecular Mechanism for Rotational Switching of the Bacterial Flagellar Motor

The bacterial flagellar motor is a remarkable nanomachine that can rapidly rotate in both counter-clockwise (CCW) and clockwise (CW) senses. The transitions between CCW and CW rotation are critical for chemotaxis, and they are controlled by a signaling protein (CheY-P) that interacts with a switch complex at the cytoplasmic side of the flagellar motor. However, the exact molecular mechanism by which CheY-P controls the motor rotational switch remains enigmatic. Here, we use the Lyme disease spirochete, Borrelia burgdorferi, as the model system to dissect the mechanism underlying flagellar rotational switching. We first determined high resolution in situ motor structures in the cheX and cheY3 mutants in which motors are genetically locked in CCW or CW rotation. The structures showed that the CheY3 protein of B. burgdorferi interacts directly with the FliM protein of the switch complex in a phosphorylation-dependent manner. The binding of CheY3-P to FliM induces a major remodeling of the switch protein FliG2 that alters its interaction with the torque generator. Because the remodeling of FliG2 is directly correlated with the rotational direction, our data lead to a model for flagellar function in which the torque generator rotates in response to an inward flow of H+ driven by the proton motive force. Rapid conformational changes of FliG2 allow the switch complex to interact with opposite sides of the rotating torque generator, thereby facilitating rotational switching between CW and CCW.

microbiology↗

bioRxiv2019

In situ structures of periplasmic flagella in Borrelia reveals conformational changes essential for flagellar rotation

The bacterial flagellar motor is a molecular machine that rotates the flagellar filament at high speed. Torque is generated by the stator-rotor interaction coupled to an ion flux through the torque-generating stator. Here, we employed cryo-electron tomography to visualize the intact flagellar motor in the Lyme disease spirochete Borrelia burgdorferi. By analysis of the motor structures of wild-type and stator mutants, we localize the torque-generating units precisely and determine three-dimensional structure of the stator and its interactions with the rotor. Our study shows that the cytoplasmic domains of the stator are packed regularly around the circumference of the flagellar C-ring. The stator-rotor interaction induces a profound conformational change in the C-ring. Analysis of the motors of a less motile motB-D24E mutant and a non-motile motB-D24N mutant, in which the proton translocation is reduced and blocked, respectively, provides evidence that the conformational change of the C-ring is essential for flagellar rotation.

microbiology↗

bioRxiv2018

In situ structures of periplasmic flagella reveal a distinct cytoplasmic ATPase complex in Borrelia burgdorferi

Periplasmic flagella are essential for the distinct morphology and motility of spirochetes. A flagella-specific Type III secretion system (fT3SS) composed of a membrane-bound export apparatus and a cytosolic ATPase complex is responsible for the assembly of the periplasmic flagella. Here, we combine cryo-electron tomography and mutagenesis approaches to characterize the fT3SS machine in the Lyme disease spirochete Borrelia burgdorferi. We define the fT3SS machine by systematically characterizing mutants lacking key component genes. We discover that a distinct cytosolic ATPase complex is attached to the flagellar C-ring through multiple spoke-like linkers. The ATPase complex not only strengthens structural rigidity of the C-ring, but also undergoes conformational changes in concert with flagellar rotation. Our studies provide structural framework to uncover the unique mechanisms underlying assembly and rotation of the periplasmic flagella and may provide the bases for the development of novel therapeutic strategies against several pathogenic spirochetes.

microbiology↗