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bioRxiv · 10.64898/2026.07.02.736100

A structural trade-off balances mechanical resilience and supramolecular adaptability in type IV pili

Tsai, C.-N. G.·Le Blanc, L.·Elgebely, F. M. F.·Al-Mayyah, Z.·Nilges, M.·Persat, A.·Karami, Y.
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Abstract

Biological machines operate under mechanical load, requiring architectures that simultaneously resist force and remain functionally dynamic. Type IV pili (T4P) are bacterial filaments that experience large tensile forces during motor-driven retraction. Here, we combine cryo-electron microscopy, molecular dynamics simulations, optical tweezers, and functional analyses to define the structural basis of T4P mechanical adaptation. We determined a 2.8 [A] cryo-EM structure of the Pseudomonas aeruginosa T4P and integrated it with comparative all-atom simulations across six bacterial strains to identify a conserved force-bearing electrostatic network. Simulations predicted that this network tunes filament elasticity under load, a finding validated by single-filament force spectroscopy. Rewiring these interactions experimentally produced hyper-rigid pili that assembled normally but exhibited impaired twitching motility. Together, our findings uncover a structural trade-off between force-resistant architecture and reversible supramolecular adaptability.

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Tsai, C.-N. G., Le Blanc, L., Elgebely, F. M. F., Al-Mayyah, Z., Nilges, M., Persat, A., Karami, Y.. 2026-07-04. A structural trade-off balances mechanical resilience and supramolecular adaptability in type IV pili. https://doi.org/10.64898/2026.07.02.736100

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