<i>De novo</i> phasing with X-ray laser reveals mosquito larvicide BinAB structure [A potent binary mosquito larvicide revealed by <i>de novo</i> phasing with an X-ray free-electron laser] [electronic resource]
Environmental Biotechnology;Protein Delivery;Nanocrystallography.
Saved in:
| Online Access: |
Online Access (via OSTI) |
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| Corporate Author: | |
| Format: | Government Document Electronic eBook |
| Language: | English |
| Published: |
Washington, D.C. : Oak Ridge, Tenn. :
United States. Department of Energy. ; distributed by the Office of Scientific and Technical Information, U.S. Department of Energy,
2016.
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| Subjects: |
| Summary: | Environmental Biotechnology;Protein Delivery;Nanocrystallography. |
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| 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 <i>Lysinibacillus sphaericus</i> BinAB solved <i>de novo</i> 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. Furthermore, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation. |
| Item Description: | Published through SciTech Connect. 09/28/2016. "nature19825" Nature (London) 539 7627 ISSN 0028-0836 AM. Jacques -Philippe Colletier; Michael R. Sawaya; Mari Gingery; Jose A. Rodriguez; Duilio Cascio; Aaron S. Brewster; Tara Michels-Clark; Robert H. Hice; Nicolas Coquelle; Sébastien Boutet; Garth J. Williams; Marc Messerschmidt; Daniel P. DePonte; Raymond G. Sierra; Hartawan Laksmono; Jason E. Koglin; Mark S. Hunter; Hyun -Woo Park; Monarin Uervirojnangkoorn; Dennis K. Bideshi; Axel T. Brunger; Brian A. Federici; Nicholas K. Sauter; David S. Eisenberg. |
| Physical Description: | p. 43-47 : digital, PDF file. |