4H56

Crystal structure of the Clostridium perfringens NetB toxin in the membrane inserted form

Summary for 4H56

• Entry DOI: 10.2210/pdb4h56/pdb
• Descriptor: Necrotic enteritis toxin B (1 entity in total)
• Functional Keywords: beta barrel, pore forming toxin, necrotic enteritis, extracellular and membrane, toxin
• Biological source: Clostridium perfringens
• Total number of polymer chains: 14
• Total formula weight: 469115.33

Authors

Savva, C.G.,Fernandes da Costa, S.P.,Bokori-Brown, M.,Naylor, C.,Cole, A.R.,Moss, D.S.,Titball, R.W.,Basak, A.K. (deposition date: 2012-09-18, release date: 2012-12-26, Last modification date: 2023-09-20)

Primary citation

Savva, C.G.,Fernandes da Costa, S.P.,Bokori-Brown, M.,Naylor, C.E.,Cole, A.R.,Moss, D.S.,Titball, R.W.,Basak, A.K.
Molecular Architecture and Functional Analysis of NetB, a Pore-forming Toxin from Clostridium perfringens.
J.Biol.Chem., 288:3512-3522, 2013

PubMed Abstract: NetB is a pore-forming toxin produced by Clostridium perfringens and has been reported to play a major role in the pathogenesis of avian necrotic enteritis, a disease that has emerged due to the removal of antibiotics in animal feedstuffs. Here we present the crystal structure of the pore form of NetB solved to 3.9 Å. The heptameric assembly shares structural homology to the staphylococcal α-hemolysin. However, the rim domain, a region that is thought to interact with the target cell membrane, shows sequence and structural divergence leading to the alteration of a phosphocholine binding pocket found in the staphylococcal toxins. Consistent with the structure we show that NetB does not bind phosphocholine efficiently but instead interacts directly with cholesterol leading to enhanced oligomerization and pore formation. Finally we have identified conserved and non-conserved amino acid positions within the rim loops that significantly affect binding and toxicity of NetB. These findings present new insights into the mode of action of these pore-forming toxins, enabling the design of more effective control measures against necrotic enteritis and providing potential new tools to the field of bionanotechnology.

PubMed: 23239883
DOI: 10.1074/jbc.M112.430223

Experimental method

X-RAY DIFFRACTION (3.9 Å)