5FOY

De novo structure of the binary mosquito larvicide BinAB at pH 7

Summary for 5FOY

• Entry DOI: 10.2210/pdb5foy/pdb
• Related: 5FOZ
• Descriptor: 41.9 KDA INSECTICIDAL TOXIN, LARVICIDAL TOXIN 51 KDA PROTEIN (3 entities in total)
• Functional Keywords: toxin, binab insecticidal toxin, pore forming toxin, xfel, serial femtosecond crystallography, de novo miras phasing, in vivo crystals
• Biological source: LYSINIBACILLUS SPHAERICUS; More
• Total number of polymer chains: 2
• Total formula weight: 93442.48

Authors

Colletier, J.P.,Sawaya, M.R.,Gingery, M.,Rodriguez, J.A.,Cascio, D.,Brewster, A.S.,Michels-Clark, T.,Boutet, S.,Williams, G.J.,Messerschmidt, M.,DePonte, D.P.,Sierra, R.G.,Laksmono, H.,Koglin, J.E.,Hunter, M.S.,W Park, H.,Uervirojnangkoorn, M.,Bideshi, D.L.,Brunger, A.T.,Federici, B.A.,Sauter, N.K.,Eisenberg, D.S. (deposition date: 2015-11-26, release date: 2016-10-05, Last modification date: 2024-11-13)

Primary citation

Colletier, J.,Sawaya, M.R.,Gingery, M.,Rodriguez, J.A.,Cascio, D.,Brewster, A.S.,Michels-Clark, T.,Hice, R.H.,Coquelle, N.,Boutet, S.,Williams, G.J.,Messerschmidt, M.,Deponte, D.P.,Sierra, R.G.,Laksmono, H.,Koglin, J.E.,Hunter, M.S.,Park, H.,Uervirojnangkoorn, M.,Bideshi, D.K.,Brunger, A.T.,Federici, B.A.,Sauter, N.K.,Eisenberg, D.S.
De Novo Phasing with X-Ray Laser Reveals Mosquito Larvicide Binab Structure.
Nature, 539:43-, 2016

PubMed Abstract: BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals-50 unit cells per edge, on average-has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine- and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation.

PubMed: 27680699
DOI: 10.1038/NATURE19825

Experimental method

X-RAY DIFFRACTION (2.25 Å)