Year: 2026
Type: preprint
Abstract: The Lyme disease spirochete Borreliella burgdorferi possesses bipolar periplasmic flagella that are essential for its distinctive flat-wave morphology, motility, and infectivity. However, how the molecular architecture of these flagella contributes to spirochetal morphology and motility remains poorly understood. Here, using in situ single-particle cryo-electron microscopy, we determine near-atomic structures of native periplasmic flagellar filaments and reveal two distinct architectures: half-sheathed and unsheathed. We show that the spirochete-specific protein FlaA forms an asymmetric sheath along the convex surface of the conserved FlaB filament core, with sheath assembly restricted to the proximal filament region near the flagellar motor. Atomic models reveal that FlaA anchors to the FlaB core through specific interactions with two surface-exposed loops, while genetic and motility analyses demonstrate distinct roles for these loops in maintaining cell morphology and motility. Structural comparisons reveal that the FlaB core possesses intrinsic curvature and supercoiling, which are substantially amplified by asymmetric FlaA assembly. These findings support a model in which localized FlaA sheath assembly reinforces the proximal filament and potentially modulates its mechanical properties. Together, our results uncover a previously unrecognized mechanism by which asymmetric sheath assembly enhances flagellar supercoiling, providing a molecular basis for understanding the distinctive morphology and motility of spirochetes. Significance The Lyme disease spirochete Borreliella burgdorferi relies on periplasmic flagella for its distinctive morphology and motility, but how filament architecture contributes to these properties remains unclear. Using in situ cryo-electron microscopy, we reveal that the spirochete-specific protein FlaA forms an asymmetric sheath around the FlaB filament core exclusively near the cell poles. FlaA anchors to flexible surface loops of FlaB through specific molecular interactions, while genetic analyses reveal distinct roles for these loops in maintaining cell morphology and motility. Asymmetric FlaA assembly amplifies the intrinsic supercoiling of the FlaB core, potentially modifying filament mechanics near the motor. These findings reveal how localized, asymmetric sheath assembly contributes to the distinctive morphology and motility of spirochetes.
Language: English
Subfield: Structural Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222794679