Oral Presentation The 5th Prato Conference on Pore Forming Proteins 2021

Structure and activity of a distinct class of toxins: Vip proteins from Bacillus thuringiensis. (#6)

Colin Berry 1 , Matthew J Byrne 2 , Matthew G Iadanza 2 , Marcos Arribas Perez 2 , Daniel P Maskell 2 , Rachel M George 2 , Emma L Hesketh 2 , Paul A Beales 2 , Marc D Zack 3 , Rebecca F Thompson 2
  1. Cardiff University, Cardiff, United Kingdom
  2. University of Leeds, Leeds
  3. Corteva Agriscience, Indianapolis

Members of the Vip3 family of toxins from Bacillus thuringiensis are selectively active against several members of the insect order Lepidoptera (butterflies and moths).  With the emergence of insect resistance to current insecticidal proteins, Vip3 is being used increasingly in transgenic plants to control pest species.  Until recently, however, little was known of the structure/function of this protein class.  Several recent structures have thrown light on the domain architecture and mechanism of action of these proteins.  Each protein is composed of 5 domains, which, despite showing no significant sequence identity, exhibit structural homology with domains seen in the 3-domain Cry class of insecticidal proteins, giving potential insights into their roles in activity.  Vip3 protoxins assemble into pyramidal tetramers, assembled as a dimer of dimers, with the alpha-helical domain 1 at the apex.  On activation by proteolysis, domain 1 from each monomer is liberated to swing down to the base of the tetrameric assembly and reassociate to form an extended coiled coil stalk with a central cavity.  Cryo-electron tomography of Vip3Bc and permeabilised liposomes shows the tip of the stalk associated with the membrane.  Thus, the remodelling of the structure on activation appears to produce a membrane penetrating spike, consistent with the pore forming mechanism of action of the protein.