ClpV family Type VI secretion system ATPase (ClpV)

ClpV1-3 represents a family of three related AAA+ ATPases that are essential components of the Type VI secretion system (T6SS) in bacteria, particularly well-characterized in *Pseudomonas aeruginosa*. These proteins belong to the Clp/Hsp100 family of chaperone ATPases and play a crucial role in disassembling contracted TssBC sheath complexes following T6SS firing, allowing the system to be recycled for subsequent rounds of secretion. ClpV proteins contain characteristic structural features including an N-terminal domain with a unique helix (α0) that distinguishes them from other Hsp100 ATPases, two nucleotide-binding domains (NBD I and II) essential for ATP binding and hydrolysis, and a middle linker region. The N-terminal domain forms a hydrophobic groove that serves as the binding site for TssC proteins (sheath components). In *P. aeruginosa*, the three ClpV isoforms show high sequence similarity, particularly between ClpV2 and ClpV3, but exhibit differences in their binding pocket sizes and functional properties. ClpV3 specifically affects multiple virulence-related phenotypes including pyocyanin production, proteolytic activity, biofilm formation, and motility through modulation of second messenger levels (c-di-GMP and cAMP). These proteins represent potential antibacterial therapeutic targets as they are critical for bacterial virulence, competition, and pathogenesis, while being absent from human cells.

Other names

Type VI secretion ATPaseClpV1 (isoform 1)ClpV2 (isoform 2)ClpV3 (isoform 3)Hsp100 family ATPaseAAA+ chaperone ClpV

Not applicable as therapeutic agent (would be a target for inhibition in antibacterial therapy)