Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Bacterial cell division requires peptidoglycan hydrolases to separate daughter cells.
• PcsB is a key enzyme in Streptococcus pneumoniae cell division, recruited by the FtsEX complex.
• Previous studies indicated PcsB lacked in vitro activity and FtsEX activation was unproven.

Purpose of the Study:

• To investigate the muralytic activity of PcsB.
• To determine the crystal structure of full-length PcsB.
• To elucidate the mechanism of PcsB regulation by the FtsEX complex.

Main Methods:

• Muralytic activity assays.
• X-ray crystallography of full-length PcsB.
• Structural analysis of PcsB dimerization and its interaction with FtsEX.

Main Results:

• PcsB exhibits muralytic activity, essential for splitting the septal cross wall.
• The crystal structure reveals PcsB forms a dimer with a V-shaped coiled-coil (CC) domain.
• The CC domain acts as molecular tweezers, inhibiting the catalytic domain in an inactive state.

Conclusions:

• PcsB's catalytic activity is regulated by its dimeric structure.
• The FtsEX complex likely activates PcsB through an ATP-driven conformational change.
• This mechanism involves coordinated movements of the CC domain, releasing the catalytic domains for cell wall hydrolysis.