PDF(Pubmed)
Abstract：
Transporters are targeted by endogenous metabolites and exogenous molecules to reach cellular destinations, but it is generally not understood how different substrate classes exploit the same transporter\'s mechanism. Any disclosure of plasticity in transporter mechanism when treated with different substrates becomes critical for developing general selectivity principles in membrane transport catalysis. Using extensive molecular dynamics simulations with an enhanced sampling approach, we select the Arabidopsis sugar transporter AtSWEET13 as a model system to identify the basis for glucose versus sucrose molecular recognition and transport. Here we find that AtSWEET13 chemical selectivity originates from a conserved substrate facial selectivity demonstrated when committing alternate access, despite mono-/di-saccharides experiencing differing degrees of conformational and positional freedom throughout other stages of transport. However, substrate interactions with structural hallmarks associated with known functional annotations can help reinforce selective preferences in molecular transport.
摘要：
转运蛋白被内源性代谢物和外源性分子靶向到达细胞目的地，但通常不理解不同的底物类如何利用相同的转运机制。当用不同底物处理时,转运蛋白机制中可塑性的任何公开对于开发膜转运催化中的一般选择性原理变得至关重要。使用广泛的分子动力学模拟和增强的采样方法，我们选择拟南芥糖转运蛋白AtSWEET13作为模型系统，以确定葡萄糖与蔗糖分子识别和转运的基础。在这里，我们发现AtSWEET13化学选择性源于在进行替代访问时证明的保守底物面部选择性，尽管单/二糖在整个其他运输阶段经历不同程度的构象和位置自由度。然而,与已知功能注释相关的结构标志的底物相互作用可以帮助增强分子运输中的选择性偏好。
