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1.C.70 The Streptococcal Pore-forming CAMP Factor (CAMP-F) Family

Streptococcus pyogenes, S. agalastiae, S. uberis and S. canis contain related pore-forming toxins called CAMP factors. They are about 255 aas long and have a single N-terminal TMS. The S. pyogenes and S. agalactiae homologues are 60% identical. CAMP factors are hemolytic and form discrete transmembrane oligomeric pores with diameters of about 1.6 nm. Electron microscopy reveals circular membrane lesions of heterogeneous sizes, up to 12-15 nm in diameter (Lang and Palmer, 2003).   The toxin allows the passive diffusion of small molecules across the membrane. Toxic activity depends on the presence of sphingomyelin (50%, 20% and 19% in sheep, human and rabbit red blood cells, respectively).

The structure of this toxin has been determined, revealing a structural fold composed of 5 + 3-helix bundles. The N-terminal 5-helix bundle is responsible for membrane permeabilization, whereas the C-terminal 3-helix bundle is likely responsible for host receptor binding. The C-terminal domain inhibited the activity of both full-length toxin and its N-terminal domain. The linker region is highly conserved and has a conserved DLXXXDXAT sequence motif. This linker region  interacted with both terminal CAMP factor domains, and mutagenesis disclosed that the conserved sequence motif is required for CAMP factor's co-hemolytic activity (Jin et al. 2018).



References associated with 1.C.70 family:

Jin, T., E. Brefo-Mensah, W. Fan, W. Zeng, Y. Li, Y. Zhang, and M. Palmer. (2018). Crystal structure of the CAMP factor provides insights into its membrane-permeabilizing activity. J. Biol. Chem. 293: 11867-11877. 29884770
Lang, S. and M. Palmer. (2003). Characterization of Streptococcus agalactiae CAMP factor as a pore-forming toxin. J. Biol. Chem. 278: 38167-38173. 12835325
Zafar, A., M. Stone, S. Ibrahim, Z. Parveen, Z. Hasan, E. Khan, R. Hasan, J. Wain, and K. Bamford. (2011). Prevalent genotypes of meticillin-resistant Staphylococcus aureus: report from Pakistan. J. Med. Microbiol. 60: 56-62. 20884770