Structure of the competence pilus major pilin ComGC in Streptococcus pneumoniae

Area of Science:

• Microbiology
• Structural Biology
• Bacterial Pathogenesis

Background:

• Type IV pili are critical virulence factors in pathogenic bacteria, mediating functions like attachment and DNA uptake.
• In *Streptococcus pneumoniae*, type IV pili facilitate DNA acquisition during competence, but their biogenesis is poorly understood.
• The major pilin protein, ComGC, forms these competence pili, which assemble specifically during bacterial competence.

Purpose of the Study:

• To determine the high-resolution structure of the ComGC pilin protein from *Streptococcus pneumoniae*.
• To elucidate the structural basis for the assembly and function of competence-induced type IV pili in Gram-positive bacteria.

Main Methods:

• High-resolution Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the structure of an N-terminal truncated ComGC.
• Analysis of protein flexibility and dynamics was performed based on NMR data.

Main Results:

• The NMR structure of N-terminal truncated ComGC reveals a highly flexible and structurally unique type IV pilin.
• ComGC comprises three α-helical segments, forming an electronegative cavity and distinct hydrophobic/electronegative patches.
• Significant flexibility exists between the first and second α-helices, with the first helix potentially forming the pilus core and helices two and three being surface-exposed.

Conclusions:

• This is the first reported structure of a type IV pilin involved in competence-induced pilus formation in Gram-positive bacteria.
• The findings highlight the substantial structural diversity among type IV pilin proteins.
• The structural insights provide a foundation for understanding competence pili biogenesis and function in *Streptococcus pneumoniae*.