8BEY

Structure of the Lysinibacillus sphaericus Tpp49Aa1 pesticidal protein at pH 7

Summary for 8BEY

• Entry DOI: 10.2210/pdb8bey/pdb
• Related: 7QA1
• Descriptor: Cry49Aa protein (2 entities in total)
• Functional Keywords: lysinibacillus sphaericus, bacillus thuringiensis, tpp49aa1, cry48aa1, xfel, sfx, mosquitoes, culex quinquefasciatus, toxin
• Biological source: Lysinibacillus sphaericus
• Total number of polymer chains: 2
• Total formula weight: 95622.87

Authors

Williamson, L.J.,Rizkallah, P.J.,Berry, C.,Oberthur, D.,Galchenkova, M.,Yefanov, O.,Bean, R. (deposition date: 2022-10-22, release date: 2023-11-01, Last modification date: 2023-12-06)

Primary citation

Williamson, L.J.,Galchenkova, M.,Best, H.L.,Bean, R.J.,Munke, A.,Awel, S.,Pena, G.,Knoska, J.,Schubert, R.,Dorner, K.,Park, H.W.,Bideshi, D.K.,Henkel, A.,Kremling, V.,Klopprogge, B.,Lloyd-Evans, E.,Young, M.T.,Valerio, J.,Kloos, M.,Sikorski, M.,Mills, G.,Bielecki, J.,Kirkwood, H.,Kim, C.,de Wijn, R.,Lorenzen, K.,Xavier, P.L.,Rahmani Mashhour, A.,Gelisio, L.,Yefanov, O.,Mancuso, A.P.,Federici, B.A.,Chapman, H.N.,Crickmore, N.,Rizkallah, P.J.,Berry, C.,Oberthur, D.
Structure of the Lysinibacillus sphaericus Tpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX.
Proc.Natl.Acad.Sci.USA, 120:e2203241120-e2203241120, 2023

PubMed Abstract: The proteins Tpp49Aa1 and Cry48Aa1 can together act as a toxin toward the mosquito and have potential use in biocontrol. Given that proteins with sequence homology to the individual proteins can have activity alone against other insect species, the structure of Tpp49Aa1 was solved in order to understand this protein more fully and inform the design of improved biopesticides. Tpp49Aa1 is naturally expressed as a crystalline inclusion within the host bacterium, and MHz serial femtosecond crystallography using the novel nanofocus option at an X-ray free electron laser allowed rapid and high-quality data collection to determine the structure of Tpp49Aa1 at 1.62 Å resolution. This revealed the packing of Tpp49Aa1 within these natural nanocrystals as a homodimer with a large intermolecular interface. Complementary experiments conducted at varied pH also enabled investigation of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals-a crucial step in its mechanism of action. To better understand the cooperation between the two proteins, assays were performed on a range of different mosquito cell lines using both individual proteins and mixtures of the two. Finally, bioassays demonstrated Tpp49Aa1/Cry48Aa1 susceptibility of , and larvae-substantially increasing the potential use of this binary toxin in mosquito control.

PubMed: 38015839
DOI: 10.1073/pnas.2203241120

Experimental method

X-RAY DIFFRACTION (1.62 Å)