MreC-MreD structure reveals a multifaceted interface that controls MreC conformation

Area of Science:

• Microbiology
• Structural Biology
• Molecular Biology

Background:

• The peptidoglycan (PG) cell wall is essential for bacterial survival and is a key antibiotic target.
• MreD is an accessory factor of the Rod complex, responsible for PG synthesis during cell elongation, but its mechanism is poorly understood.

Purpose of the Study:

• To elucidate the structural and functional role of MreD in the bacterial Rod complex.
• To understand how MreD facilitates peptidoglycan synthesis and bacterial cell shape determination.

Main Methods:

• Determined the cryo-electron microscopy structure of *Thermus thermophilus* MreD in complex with MreC.
• Utilized single-molecule Förster Resonance Energy Transfer (FRET) to analyze MreD-MreC interactions and conformational changes.
• Investigated the in vivo effects of disrupting MreD-MreC interactions in *E. coli*.

Main Results:

• The cryo-EM structure revealed a specific interaction between a pocket on MreD and membrane-proximal regions of MreC.
• Single-molecule FRET demonstrated that MreD induces a specific conformation in MreC, priming it for Rod complex activation.
• Disruption of these MreD-MreC interactions in *E. coli* led to the abolition of Rod complex activity in vivo.

Conclusions:

• MreD plays a critical role in regulating bacterial cell shape by controlling MreC conformation within the Rod complex.
• The identified MreD-MreC interaction is essential for peptidoglycan synthesis and bacterial cell integrity.
• MreD represents a potential novel antibiotic target due to its crucial role in bacterial cell wall maintenance.