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Published on: December 17, 2013
A repulsive electrostatic mechanism for protein export through the type III secretion apparatus
Thenmalarchelvi Rathinavelan1, Lingling Zhang, Wendy L Picking
1Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas, USA.
Shigella flexneri bacteria inject proteins using a type III secretion system. Simulations reveal a repulsive electrostatic mechanism, driven by negative charges, facilitates protein export through the needle channel.
Area of Science:
- Microbiology
- Structural Biology
- Biophysics
Background:
- Gram-negative bacteria use type III secretion systems (T3SS) to infect host cells.
- The T3SS needle complex facilitates effector protein translocation.
- MxiH is the needle protein essential for T3SS needle assembly.
Purpose of the Study:
- To investigate the export mechanism of the MxiH needle protein through the T3SS needle.
- To elucidate the role of electrostatic interactions in protein translocation via T3SS.
Main Methods:
- Steered molecular dynamics simulations in implicit solvent were employed.
- Analysis of MxiH protein conformations and channel electrostatic potential.
Main Results:
- MxiH export involves a screwlike rotation of helix-turn-helix conformations.
- The T3SS needle channel exhibits an electronegative potential, creating an entry barrier but aiding ejection.
- Bacterial effector proteins also possess electronegative surface patches.
Conclusions:
- A repulsive electrostatic mechanism is proposed for protein translocation through the T3SS.
- ATPase activity and/or proton motive force may energize this translocation process.
- This mechanism could apply to other protein/nucleic acid transport systems.
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