Cytotoxic necrotising factor family explained

Symbol:CNF1
CNF1
Pfam:PF05785
Interpro:IPR008430
Scop:1hzg

In molecular biology, the cytotoxic necrotising factor family of proteins includes bacterial cytotoxic necrotising factor proteins and the related dermonecrotic toxin (DNT) from Bordetella species. Cytotoxic necrotizing factor 1 (CNF1) is a toxin whose structure from Escherichia coli revealed a 4-layer alpha/beta/beta/alpha structure containing mixed beta-sheets.[1] CNF1 is expressed in strains of E. coli causing uropathogenic and neonatal meningitis. CNF1 alters host cell actin cytoskeleton and promotes bacterial invasion of the blood–brain barrier endothelial cells.[2] CNF1 belongs to a unique group of large cytotoxins that cause constitutive activation of Rho guanosine triphosphatases (GTPases), which are key regulators of the actin cytoskeleton .

Bordetella dermonecrotic toxin (DNT) stimulates the assembly of actin stress fibres and focal adhesions by deamidating or polyaminating Gln63 of the small GTPase Rho. DNT is an A-B toxin composed of an N-terminal receptor-binding (B) domain and a C-terminal enzymatically active (A) domain.[3]

Notes and References

  1. Buetow L, Flatau G, Chiu K, Boquet P, Ghosh P . Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1 . Nat. Struct. Biol. . 8 . 7 . 584–8 . July 2001 . 11427886 . 10.1038/89610 . 19515513 .
  2. Wang. Ming-Hsien. Kim. Kwang. Cytotoxic Necrotizing Factor 1 Contributes to Escherichia coli Meningitis. Toxins. 5. 11. 2013. 2270–2280. 2072-6651. 10.3390/toxins5112270. 24284829. 3847726. free.
  3. Matsuzawa T, Kashimoto T, Katahira J, Horiguchi Y . Identification of a receptor-binding domain of Bordetella dermonecrotic toxin . Infect. Immun. . 70 . 7 . 3427–32 . July 2002 . 12065482 . 128056 . 10.1128/iai.70.7.3427-3432.2002.