TcpA from the Clostridium perfringens plasmid pCW3 is more closely related to the DNA translocase FtsK than to coupling proteins

Conjugative DNA transfer is a major factor in the dissemination of antibiotic resistance and virulence genes. In the Gram-positive pathogen Clostridium perfringens, the majority of conjugative plasmids share the conserved tcp locus that governs the assembly of the transfer system. Here, we describe multiple structures of the coupling protein TcpA, an essential ATPase that is suggested to provide the mechanical force to propel the DNA through the transfer apparatus. The structures of TcpA in the presence and absence of nucleotides revealed conformational rearrangements and highlight a crucial role for the unstructured C terminus. Our findings reveal that TcpA shares most structural similarity with the FtsK DNA translocase, a central compo-nent of the bacterial cell division machinery. Our structural data suggest that conjugation in C. perfringens may have evolved from the bacterial chromosome segregation system and, accordingly, suggest the possi-bility that double-stranded DNA is transferred through the Tcp conjugation apparatus.

Automated summary

This study describes a major DNA transfer system in the Gram-positive pathogen Clostridium perfringens which participates in the dissemination of antibiotic resistance and virulence genes. The coupling protein TcpA, an essential ATPase, is proposed to provide the mechanical force for DNA transfer. Structural analysis reveals that TcpA shares structural similarities with the FtsK DNA translocase, suggesting a possible evolution of conjugation in C. perfringens from bacterial chromosome segregation.