Abstract
Very little is known about how fimbriae of Bacteroidetes bacteria are assembled. To shed more light on this process, we solved the crystal structures of the shaft protein Mfa1, the regulatory protein Mfa2, and the tip protein Mfa3 from the periodontal pathogen Porphyromonas gingivalis. Together these build up part of the Mfa1 fimbria and represent three of the five proteins, Mfa1-5, encoded by the mfa1 gene cluster. Mfa1, Mfa2 and Mfa3 have the same overall fold i.e., two β-sandwich domains. Upon polymerization, the first β-strand of the shaft or tip protein is removed by indigenous proteases. Although the resulting void is expected to be filled by a donor-strand from another fimbrial protein, the mechanism by which it does so is still not established. In contrast, the first β-strand in Mfa2, the anchoring protein, is firmly attached by a disulphide bond and is not cleaved. Based on the structural information, we created multiple mutations in P. gingivalis and analysed their effect on fimbrial polymerization and assembly in vivo. Collectively, these data suggest an important role for the C-terminal tail of Mfa1, but not of Mfa3, affecting both polymerization and maturation of downstream fimbrial proteins.
Highlights
Humans co-exist with microorganisms that play significant roles in our biology
While it is probable that the FimA and Mfa[1] fimbria have multiple binding targets, it has so far been shown that FimA binds glyceraldehyde 3-phosphate dehydrogenase on the surfaces of oral streptococci[15] and that Mfa[1] interacts with a specific region of the C-terminal domain of the streptococcal SspB/A adhesins[16]
Fimbrial proteins and their structures are well studied in Gram-negative bacteria such as Escherichia coli or Yersinia pestis[17], and in particular, their role in the polymerization of the type-1 fimbria, which is dependent on the chaperone-usher pathway[18]
Summary
Humans co-exist with microorganisms that play significant roles in our biology. The largest bacterial population is found in the gut, where species of Bacteroidetes are the most common Gram-negative anaerobes[1]. While it is probable that the FimA and Mfa[1] fimbria have multiple binding targets, it has so far been shown that FimA binds glyceraldehyde 3-phosphate dehydrogenase on the surfaces of oral streptococci[15] and that Mfa[1] interacts with a specific region of the C-terminal domain of the streptococcal SspB/A adhesins[16] Fimbrial proteins and their structures are well studied in Gram-negative bacteria such as Escherichia coli or Yersinia pestis[17], and in particular, their role in the polymerization of the type-1 fimbria, which is dependent on the chaperone-usher pathway[18]. We combined the structural information regarding these proteins with in vitro and in vivo phenotypic analyses, thereby gaining valuable new insight into the assembly process of the Mfa[1] fimbria
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