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Role of substrate recognition in modulating strigolactone receptor selectivity in witchweed.
bioRxiv - Plant Biology Pub Date : 2020-07-29 , DOI: 10.1101/2020.07.28.225722
Jiming Chen , Alexandra White , David C. Nelson , Diwakar Shukla

Witchweed, or Striga hermonthica, is a parasitic weed that destroys billions of dollars worth of crops globally every year. Its germination is stimulated by strigolactones exuded by its host plants. Despite high sequence, structure, and ligand binding site conservation across different plant species, one strigolactone receptor in witchweed (ShHTL7) uniquely exhibits a picomolar EC50 for downstream signaling. Previous biochemical and structural analyses have hypothesized that this unique ligand sensitivity can be attributed to a large binding pocket volume in ShHTL7 resulting in enhanced ability to bind substrates. Additional structural details of the substrate binding process can help explain its role in modulating the ligand selectivity. Using long-timescale molecular dynamics simulations, we demonstrate that mutations at the entrance of the binding pocket facilitate a more direct ligand binding pathway to ShHTL7, whereas hydrophobicity at the binding pocket entrance results in a stable "anchored" state. We also demonstrate that several residues on the D-loop of AtD14 stabilize catalytically inactive conformations. Finally, we show that strigolactone selectivity is not modulated by binding pocket volume. Our results indicate that while ligand binding is not the sole modulator of strigolactone receptor selectivity, it is a significant contributing factor. These results can be used to inform the design of selective antagonists for strigolactone receptors in witchweed.

中文翻译:

底物识别在调节草甘膦内酯内酯受体选择性中的作用。

巫婆或Striga hermonthica是一种寄生性杂草,每年在全球范围内破坏价值数十亿美元的农作物。它的发芽受到其宿主植物渗出的strigolactones的刺激。尽管跨不同植物物种具有较高的序列,结构和配体结合位点保守性,但金缕梅中的一种草甘膦内酯受体(ShHTL7)独特地表现出皮摩尔EC50用于下游信号传导。以前的生物化学和结构分析已假设,这种独特的配体敏感性可归因于ShHTL7中的大结合口袋体积,从而增强了结合底物的能力。底物结合过程的其他结构细节可以帮助解释其在调节配体选择性中的作用。使用长期分子动力学模拟,我们证明在结合袋的入口处的突变促进了更直接的配体与ShHTL7的结合途径,而在结合袋的入口处的疏水性导致稳定的“锚定”状态。我们还证明了AtD14 D环上的几个残基稳定了催化惰性构象。最后,我们证明了链格内酯的选择性不受结合口袋体积的调节。我们的结果表明,虽然配体结合不是Strigolactone受体选择性的唯一调节剂,但它是一个重要的促成因素。这些结果可用于设计紫草中草甘酸内酯受体的选择性拮抗剂。
更新日期:2020-07-30
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