Structural Basis of Pilus Anchoring by the Ancillary Pilin RrgC of Streptococcus pneumoniae

• Published in: The Journal of biological chemistry 2014-06, Vol.289 (24), p.16988-16997
• Main Authors: Shaik, Md Munan, Maccagni, Amandine, Tourcier, Guillaume, Di Guilmi, Anne Marie, Dessen, Andréa
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Aminoacyltransferases; Aminoacyltransferases - metabolism; Bacterial Adhesion; Bacterial Proteins; Bacterial Proteins - metabolism; Bacterial Toxin; Biochemistry, Molecular Biology; Crystal Structure; Cysteine Endopeptidases; Cysteine Endopeptidases - metabolism; Fimbriae Proteins; Fimbriae Proteins - chemistry; Fimbriae Proteins - genetics; Fimbriae Proteins - metabolism; Fimbriae, Bacterial; Fimbriae, Bacterial - chemistry; Fimbriae, Bacterial - metabolism; Infectious Disease; Life Sciences; Molecular Sequence Data; Protein Binding; Protein Structure and Folding; Protein Structure, Tertiary; Streptococcus pneumoniae; Streptococcus pneumoniae - chemistry; Streptococcus pneumoniae - metabolism; Structural Biology; Virulence Factor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.555854

Pili are surface-attached, fibrous virulence factors that play key roles in the pathogenesis process of a number of bacterial agents. Streptococcus pneumoniae is a causative agent of pneumonia and meningitis, and the appearance of drug-resistance organisms has made its treatment challenging, especially in developing countries. Pneumococcus-expressed pili are composed of three structural proteins: RrgB, which forms the polymerized backbone, RrgA, the tip-associated adhesin, and RrgC, which presumably associates the pilus with the bacterial cell wall. Despite the fact that the structures of both RrgA and RrgB were known previously, structural information for RrgC was still lacking, impeding the analysis of a complete model of pilus architecture. Here, we report the structure of RrgC to 1.85 Å and reveal that it is a three-domain molecule stabilized by two intradomain isopeptide bonds. RrgC does not depend on pilus-specific sortases to become attached to the cell wall; instead, it binds the preformed pilus to the peptidoglycan by employing the catalytic activity of SrtA. A comprehensive model of the type 1 pilus from S. pneumoniae is also presented. Background: RrgC is a key component of the pneumococcal pilus, a virulence factor that plays an important role in pathogenesis. Results: RrgC folds into three independent domains and requires the housekeeping sortase for surface association. Conclusion: The rod-like structure of RrgC suggests that it stably bridges peptidoglycan and pilus fiber. Significance: A complete model of the pneumococcal pilus reveals a multidomain, flexible assembly.