Texas 2-Step: A new Model for YcgR::c-di-GMP Action at the Flagellar Motor

Area of Science:

• Microbiology
• Molecular Biology
• Biophysics

Background:

• YcgR is a cyclic-GMP (c-di-GMP) effector protein influencing bacterial motility.
• Its precise mechanism for inhibiting chemotaxis and swimming speed in E. coli and Salmonella remains unclear.
• Previous studies proposed YcgR acts on either the flagellar rotor or stator, with conflicting results.

Purpose of the Study:

• To elucidate the mechanism by which YcgR inhibits bacterial chemotaxis and swimming speed.
• To propose and test a novel model for YcgR function based on recent structural data.

Main Methods:

• Utilized genetic, biochemical, and structural data, including cryo-electron microscopy (cryo-EM) structures.
• Proposed the "Texas 2-Step model" for YcgR action.
• Provided experimental evidence supporting the initial step of the proposed model.

Main Results:

• The Texas 2-Step model posits YcgR interacts with the MotA subunit of the flagellar stator in the counter-clockwise (CCW) conformation.
• This interaction occurs when stators are outside the C ring, preceding YcgR's delivery to FliG.
• Evidence supports the initial interaction between YcgR and MotA, a key step in the proposed mechanism.

Conclusions:

• The Texas 2-Step model offers a unified explanation for YcgR's effects on flagellar motor bias and speed.
• The findings provide a mechanistic basis for YcgR's inhibitory role in bacterial motility.
• This study generates new, testable hypotheses regarding flagellar motor regulation by c-di-GMP effectors.