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A glycine-rich PE_PGRS protein governs mycobacterial actin-based motility

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  • Norbert S. Hill

    (University of California)

  • Matthew D. Welch

    (University of California)

Abstract

Many key insights into actin regulation have been derived through examining how microbial pathogens intercept the actin cytoskeleton during infection. Mycobacterium marinum, a close relative of the human pathogen Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. However, the mycobacterial factor that commandeers actin polymerization has remained elusive. Here, we report the identification and characterization of the M. marinum actin-based motility factor designated mycobacterial intracellular rockets A (MirA), which is a member of the glycine-rich PE_PGRS protein family. MirA contains an amphipathic helix to anchor into the mycobacterial outer membrane and, surprisingly, also the surface of host lipid droplet organelles. MirA directly binds to and activates the host protein N-WASP to stimulate actin polymerization through the Arp2/3 complex, directing both bacterial and lipid droplet actin-based motility. MirA is dissimilar to known N-WASP activating ligands and may represent a new class of microbial and host actin regulator. Additionally, the MirA-N-WASP interaction represents a model to understand how the enigmatic PE_PGRS proteins contribute to mycobacterial pathogenesis.

Suggested Citation

  • Norbert S. Hill & Matthew D. Welch, 2022. "A glycine-rich PE_PGRS protein governs mycobacterial actin-based motility," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31333-0
    DOI: 10.1038/s41467-022-31333-0
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    2. Hiroaki Miki & Takuya Sasaki & Yoshimi Takai & Tadaomi Takenawa, 1998. "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP," Nature, Nature, vol. 391(6662), pages 93-96, January.
    3. Hui-Chun Cheng & Brian M. Skehan & Kenneth G. Campellone & John M. Leong & Michael K. Rosen, 2008. "Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspFU," Nature, Nature, vol. 454(7207), pages 1009-1013, August.
    4. Nathan A. Sallee & Gonzalo M. Rivera & John E. Dueber & Dan Vasilescu & R. Dyche Mullins & Bruce J. Mayer & Wendell A. Lim, 2008. "The pathogen protein EspFU hijacks actin polymerization using mimicry and multivalency," Nature, Nature, vol. 454(7207), pages 1005-1008, August.
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