The importance of electrostatic potential in the interaction of sweet proteins with the sweet taste receptor
The importance of electrostatic potential in the interaction of sweet proteins with the sweet taste receptor
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DOI：
10.1016/j.jmb.2006.05.020
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发表时间：
2006-07-07
影响因子：
5.6
通讯作者：
Temussi, Piero A.
中科院分区：
文献类型：
--
作者：
Esposito, Veronica;Gallucci, Roberta;Temussi, Piero A.
除了许多小分子质量甜味剂外，自然界中还有一些甜蛋白。甜蛋白的分子体积与普通甜味剂的分子体积如此不同，以至于很难理解像蛋白质这样大的分子如何激活专为容纳小分子而设计的受体。我们最近的研究表明，甜蛋白可以通过一种称为“楔形模型”的相互作用机制激活甜受体，在这种机制中，蛋白质以其结构的楔形表面适应受体的大腔。为了证实这个模型，我们设计了；表达并鉴定了7个MNEI（一种单链monellin）突变体。相互作用表面的3个不带电残基Met42、Tyr63和Tyr65分别转化为酸性残基和碱性残基，而关键的酸性残基Asp68则转化为碱性残基。作为一般趋势，我们观察到负电荷的增加比正电荷的增加对甜味的危害更大。此外，我们表明，通过仔细选择MNEI和受体之间界面中心的残基，甚至有可能增加MNEI的甜度。这些结果与楔形模型完全一致。(c) 2006 Elsevier Ltd.版权所有。
In addition to many small molecular mass sweeteners there are in nature a few sweet proteins. The molecular volume of sweet proteins is so different from that of common sweeteners that it was difficult to understand how molecules as large as proteins can activate a receptor designed to host small molecules. We have recently shown that sweet proteins can activate the sweet receptor by a mechanism of interaction, called "wedge model", in which proteins fit a large cavity of the receptor with wedge-shaped surfaces of their structures. In order to substantiate this model we have designed; expressed and characterized seven mutants of MNEI, a single chain monellin. Three uncharged residues of the interaction surface, Met42, Tyr63 and Tyr65, were changed either into acidic or basic residues whereas Asp68, a key acidic residue, was changed into a basic one. As a general trend, we observe that an increase of the negative charge is much more detrimental for sweetness than an increase of positive charge. In addition we show that by a careful choice of a residue at the center of the interface between MNEI and receptor, it is possible even to increase the sweetness of MNEI. These results are fully consistent with the wedge model. (c) 2006 Elsevier Ltd. All rights reserved.