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==Native structure of mosquitocidal Cyt1A protoxin obtained by Serial Femtosecond Crystallography on in vivo grown crystals at pH 7==
==Native structure of mosquitocidal Cyt1A protoxin obtained by Serial Femtosecond Crystallography on in vivo grown crystals at pH 7==
<StructureSection load='6t14' size='340' side='right'caption='[[6t14]]' scene=''>
<StructureSection load='6t14' size='340' side='right'caption='[[6t14]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T14 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6T14 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6t14]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacti Bacti]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T14 FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6t14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t14 OCA], [http://pdbe.org/6t14 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t14 RCSB], [http://www.ebi.ac.uk/pdbsum/6t14 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t14 ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyt1Aa, cytA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1430 BACTI])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t14 OCA], [https://pdbe.org/6t14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t14 RCSB], [https://www.ebi.ac.uk/pdbsum/6t14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t14 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/CT1AA_BACTI CT1AA_BACTI]] Kills the larvae of dipteran insects by making pores in the epithelial cell membrane of the insect midgut. Acts on mosquitos and black flies.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyt1Aa is the one of four crystalline protoxins produced by mosquitocidal bacterium Bacillus thuringiensis israelensis (Bti) that has been shown to delay the evolution of insect resistance in the field. Limiting our understanding of Bti efficacy and the path to improved toxicity and spectrum has been ignorance of how Cyt1Aa crystallizes in vivo and of its mechanism of toxicity. Here, we use serial femtosecond crystallography to determine the Cyt1Aa protoxin structure from sub-micron-sized crystals produced in Bti. Structures determined under various pH/redox conditions illuminate the role played by previously uncharacterized disulfide-bridge and domain-swapped interfaces from crystal formation in Bti to dissolution in the larval mosquito midgut. Biochemical, toxicological and biophysical methods enable the deconvolution of key steps in the Cyt1Aa bioactivation cascade. We additionally show that the size, shape, production yield, pH sensitivity and toxicity of Cyt1Aa crystals grown in Bti can be controlled by single atom substitution.
Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade.,Tetreau G, Banneville AS, Andreeva EA, Brewster AS, Hunter MS, Sierra RG, Teulon JM, Young ID, Burke N, Grunewald TA, Beaudouin J, Snigireva I, Fernandez-Luna MT, Burt A, Park HW, Signor L, Bafna JA, Sadir R, Fenel D, Boeri-Erba E, Bacia M, Zala N, Laporte F, Despres L, Weik M, Boutet S, Rosenthal M, Coquelle N, Burghammer M, Cascio D, Sawaya MR, Winterhalter M, Gratton E, Gutsche I, Federici B, Pellequer JL, Sauter NK, Colletier JP Nat Commun. 2020 Mar 2;11(1):1153. doi: 10.1038/s41467-020-14894-w. PMID:32123169<ref>PMID:32123169</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6t14" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacti]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Andreeva E]]
[[Category: Andreeva, E]]
[[Category: Banneville AS]]
[[Category: Banneville, A S]]
[[Category: Boutet S]]
[[Category: Boutet, S]]
[[Category: Brewster AS]]
[[Category: Brewster, A S]]
[[Category: Cascio D]]
[[Category: Cascio, D]]
[[Category: Colletier JP]]
[[Category: Colletier, J P]]
[[Category: Coquelle N]]
[[Category: Coquelle, N]]
[[Category: Hunter MS]]
[[Category: Hunter, M S]]
[[Category: Sauter NK]]
[[Category: Sauter, N K]]
[[Category: Sawaya MR]]
[[Category: Sawaya, M R]]
[[Category: Sierra RG]]
[[Category: Sierra, R G]]
[[Category: Tetreau G]]
[[Category: Tetreau, G]]
[[Category: Young ID]]
[[Category: Young, I D]]
[[Category: In vivo grown nanocrystal]]
[[Category: Mosquitocidal toxin]]
[[Category: Toxin]]

Revision as of 08:27, 28 April 2021

Native structure of mosquitocidal Cyt1A protoxin obtained by Serial Femtosecond Crystallography on in vivo grown crystals at pH 7Native structure of mosquitocidal Cyt1A protoxin obtained by Serial Femtosecond Crystallography on in vivo grown crystals at pH 7

Structural highlights

6t14 is a 1 chain structure with sequence from Bacti. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:cyt1Aa, cytA (BACTI)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CT1AA_BACTI] Kills the larvae of dipteran insects by making pores in the epithelial cell membrane of the insect midgut. Acts on mosquitos and black flies.

Publication Abstract from PubMed

Cyt1Aa is the one of four crystalline protoxins produced by mosquitocidal bacterium Bacillus thuringiensis israelensis (Bti) that has been shown to delay the evolution of insect resistance in the field. Limiting our understanding of Bti efficacy and the path to improved toxicity and spectrum has been ignorance of how Cyt1Aa crystallizes in vivo and of its mechanism of toxicity. Here, we use serial femtosecond crystallography to determine the Cyt1Aa protoxin structure from sub-micron-sized crystals produced in Bti. Structures determined under various pH/redox conditions illuminate the role played by previously uncharacterized disulfide-bridge and domain-swapped interfaces from crystal formation in Bti to dissolution in the larval mosquito midgut. Biochemical, toxicological and biophysical methods enable the deconvolution of key steps in the Cyt1Aa bioactivation cascade. We additionally show that the size, shape, production yield, pH sensitivity and toxicity of Cyt1Aa crystals grown in Bti can be controlled by single atom substitution.

Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade.,Tetreau G, Banneville AS, Andreeva EA, Brewster AS, Hunter MS, Sierra RG, Teulon JM, Young ID, Burke N, Grunewald TA, Beaudouin J, Snigireva I, Fernandez-Luna MT, Burt A, Park HW, Signor L, Bafna JA, Sadir R, Fenel D, Boeri-Erba E, Bacia M, Zala N, Laporte F, Despres L, Weik M, Boutet S, Rosenthal M, Coquelle N, Burghammer M, Cascio D, Sawaya MR, Winterhalter M, Gratton E, Gutsche I, Federici B, Pellequer JL, Sauter NK, Colletier JP Nat Commun. 2020 Mar 2;11(1):1153. doi: 10.1038/s41467-020-14894-w. PMID:32123169[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Tetreau G, Banneville AS, Andreeva EA, Brewster AS, Hunter MS, Sierra RG, Teulon JM, Young ID, Burke N, Grunewald TA, Beaudouin J, Snigireva I, Fernandez-Luna MT, Burt A, Park HW, Signor L, Bafna JA, Sadir R, Fenel D, Boeri-Erba E, Bacia M, Zala N, Laporte F, Despres L, Weik M, Boutet S, Rosenthal M, Coquelle N, Burghammer M, Cascio D, Sawaya MR, Winterhalter M, Gratton E, Gutsche I, Federici B, Pellequer JL, Sauter NK, Colletier JP. Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade. Nat Commun. 2020 Mar 2;11(1):1153. doi: 10.1038/s41467-020-14894-w. PMID:32123169 doi:http://dx.doi.org/10.1038/s41467-020-14894-w

6t14, resolution 1.86Å

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