De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure.
De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure.
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DOI：
10.1038/nature19825
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发表时间：
2016-11-03
期刊：
影响因子：
64.8
通讯作者：
Eisenberg, David S.
中科院分区：
文献类型：
--
作者：
Colletier, Jacques-Philippe;Sawaya, Michael R.;Gingery, Mari;Rodriguez, Jose A.;Cascio, Duilio;Brewster, Aaron S.;Michels-Clark, Tara;Hice, Robert H.;Coquelle, Nicolas;Boutet, Sebastien;Williams, Garth J.;Messerschmidt, Marc;DePonte, Daniel P.;Sierra, Raymond G.;Laksmono, Hartawan;Koglin, Jason E.;Hunter, Mark S.;Park, Hyun-Woo;Uervirojnangkoorn, Monarin;Bideshi, Dennis K.;Brunger, Axel T.;Federici, Brian A.;Sauter, Nicholas K.;Eisenberg, David S.
BinAB是一种天然存在的类晶体杀幼虫剂，分布在世界各地，用于防治蚊子携带的毁灭性疾病。这些晶体由同源分子BinA和BinB组成，它们在多步中毒过程中发挥不同的作用，从无害的坚固晶体转化为可溶性原毒素异源二聚体，转化为内化的成熟毒素，最后转化为有毒的寡聚体孔。晶体的小尺寸，平均每边50个晶胞，阻碍了常规方法的结构表征。在这里，我们报告的结构BinAB解决从头连续飞秒晶体学在X射线自由电子激光（XFEL）。结构揭示酪氨酸和羧酸介导的接触作为pH开关释放可溶性原毒素在碱性幼虫中肠。一个巨大的异源二聚体界面似乎负责锚定BinA受体结合BinB共内化。值得注意的是，该界面主要由前肽组成，这表明蛋白水解成熟将引发异二聚体的解离并进展到孔形成。
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 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 BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser (XFEL). 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 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.
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影响因子：
3.7
作者：
Kelker MS;Berry C;Evans SL;Pai R;McCaskill DG;Wang NX;Russell JC;Baker MD;Yang C;Pflugrath JW;Wade M;Wess TJ;Narva KE
通讯作者：
Narva KE
影响因子：
14.8
作者：
Degiacomi, Matteo T.;Lacovache, Ioan;Dal Peraro, Matteo
通讯作者：
Dal Peraro, Matteo
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444904016427
发表时间：
2004-12-01
影响因子：
2.2
作者：
Blanc, E;Roversi, P;Bricogne, G
通讯作者：
Bricogne, G
影响因子：
4.4
作者：
BOURGOUIN, C;DELECLUSE, A;SZULMAJSTER, J
通讯作者：
SZULMAJSTER, J