典型的鲜味配体诱导的 T1R1-VFT 结合相互作用和构象变化,Journal of Agricultural and Food Chemistry

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典型的鲜味配体诱导的 T1R1-VFT 结合相互作用和构象变化
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-09-13 , DOI: 10.1021/acs.jafc.2c05559
Ninglong Zhang ₁ , Zhiyong Cui ₁ , Mingyang Li ₁ , Yuxia Fan ₁ , Jing Liu ₂ , Wenli Wang ₁ , Yin Zhang ₃ , Yuan Liu ₁

Affiliation

鲜味受体 1 型成员 1/3 (T1R1/T1R3) 异二聚体具有多个配体结合位点，其中大部分位于 T1R1-捕蝇草结构域 (T1R1-VFT)。然而，T1R1-VFT/鲜味配体的关键结合过程仍然很大程度上未知。在此，我们制备了具有足够量和功能活性的 T1R1-VFT，并通过以下方法探索了其与典型鲜味分子（L-谷氨酸单钠、琥珀酸二钠、牛肉肽和 5'-单磷酸肌苷）的结合特性。多光谱技术和分子动力学模拟。结果表明，在氢键、范德华力和静电相互作用的驱动下，T1R1-VFT 以 1:1 的比例与鲜味化合物结合（化学计量相互作用）并形成 T1R1-VFT/配体复合物（静态荧光猝灭），具有弱结合亲和力（K _a值：252 ± 19 至 1169 ± 112 M ^–1）。结合过程是自发的和放热的 ( ΔG , -17.72 to -14.26 kJ mol ^–1 ; ΔH , -23.86 to -12.11 kJ mol ^–1) 并诱导 T1R1-VFT 的构象变化，这主要体现在 α-螺旋 (Δα-螺旋 < 0) 和多肽链骨架结构的轻微展开。同时，四种配体的结合稳定了 T1R1-VFT 口袋的活性构象。这项工作提供了对 T1R1-VFT/鲜味配体之间结合相互作用的深入了解，并提高了对鲜味受体如何识别特定配体分子的理解。

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Typical Umami Ligand-Induced Binding Interaction and Conformational Change of T1R1-VFT

Umami taste receptor type 1 member 1/3 (T1R1/T1R3) heterodimer has multiple ligand-binding sites, most of which are located in T1R1-Venus flytrap domain (T1R1-VFT). However, the critical binding process of T1R1-VFT/umami ligands remains largely unknown. Herein, T1R1-VFT was prepared with a sufficient amount and functional activity, and its binding characteristics with typical umami molecules (monosodium l-glutamate, disodium succinate, beefy meaty peptide, and inosine-5′-monophosphate) were explored via multispectroscopic techniques and molecular dynamics simulation. The results showed that, driven mainly by hydrogen bond, van der Waals forces, and electrostatic interactions, T1R1-VFT bound to umami compound at 1:1 (stoichiometric interaction) and formed T1R1-VFT/ligand complex (static fluorescence quenching) with a weak binding affinity (K_a values: 252 ± 19 to 1169 ± 112 M^–1). The binding process was spontaneous and exothermic (ΔG, −17.72 to −14.26 kJ mol^–1; ΔH, −23.86 to −12.11 kJ mol^–1) and induced conformational changes of T1R1-VFT, which was mainly reflected in slight unfolding of α-helix (Δα-helix < 0) and polypeptide chain backbone structure. Meanwhile, the binding of the four ligands stabilized the active conformation of the T1R1-VFT pocket. This work provides insight into the binding interaction between T1R1-VFT/umami ligands and improves understanding of how umami receptor recognizes specific ligand molecules.

更新日期：2022-09-13

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