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In Vitro and in Silico Analyses of the Adiponectin Receptor Agonistic Action of Soybean Tripeptides
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-06-15 , DOI: 10.1021/acs.jafc.2c02115
Yuna Lee 1 , Akihiro Nakano 1 , Yuki Nagasato 1 , Takashi Ichinose 2 , Toshiro Matsui 1
Affiliation  

The Tyr-Pro (YP) dipeptide can serve as an adiponectin receptor 1 (AdipoR1) agonist. We thus investigated the AdipoR1-agonistic potential of YP-related tripeptides in the soybean protein sequence. Among the 17 soybean candidate tripeptides, those elongated at the C-terminus of YP (0.1 μM YPG, 140 ± 16%; 0.1 μM YPE, 141 ± 22%; 0.1 μM YPP, 145 ± 19%; 0.1 μM YPQ, 143 ± 20%; p < 0.05) significantly promoted glucose uptake by L6 muscle myotubes, comparable to the effect of 0.1 μM AdipoRon (163 ± 52%, p < 0.05). The knockdown of AdipoR1 expression in L6 cells abrogated this effect of YPG and YPP, indicating that the two tripeptides had an AdipoR1 agonistic effect. CHARMM-GUI-aided molecular dynamics simulation in a virtual phospholipid membrane revealed that YPG and YPP were stably positioned at the binding pockets of AdipoR1 (binding free energy < −10 kcal/mol). These findings demonstrate that the tripeptides YPG and YPP, with AdipoR1 agonistic YP sequences, have alternative adiponectin-like potential via their preferential binding to AdipoR1.

中文翻译:


大豆三肽脂联素受体激动作用的体外和计算机分析



Tyr-Pro (YP) 二肽可作为脂联素受体 1 (AdipoR1) 激动剂。因此,我们研究了大豆蛋白序列中 YP 相关三肽的 AdipoR1 激动潜力。在 17 种大豆候选三肽中,YP C 端延长的三肽(0.1 μM YPG,140 ± 16%;0.1 μM YPE,141 ± 22%;0.1 μM YPP,145 ± 19%;0.1 μM YPQ,143 ± 20%; p < 0.05)显着促进 L6 肌管的葡萄糖摄取,与 0.1 μM AdipoRon 的效果相当(163 ± 52%, p < 0.05)。 L6细胞中AdipoR1表达的敲低消除了YPG和YPP的这种作用,表明这两种三肽具有AdipoR1激动作用。虚拟磷脂膜中的 CHARMM-GUI 辅助分子动力学模拟表明,YPG 和 YPP 稳定定位在 AdipoR1 的结合袋上(结合自由能 < -10 kcal/mol)。这些发现表明,具有 AdipoR1 激动性 YP 序列的三肽 YPG 和 YPP通过优先与 AdipoR1 结合而具有替代脂联素样潜力。
更新日期:2022-06-15
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