Biologically active LIL proteins built with minimal chemical diversity
Biologically active LIL proteins built with minimal chemical diversity
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DOI：
10.1073/pnas.1514230112
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发表时间：
2015-08-25
影响因子：
11.1
通讯作者：
DiMaio, Daniel
中科院分区：
文献类型：
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作者：
Heim, Erin N.;Marston, Jez L.;DiMaio, Daniel
我们已经构建了26个氨基酸的跨膜蛋白，它们特异性地转化细胞，但仅由两个不同的氨基酸组成。大多数蛋白质是氨基酸的长聚合物，具有20个或更多个化学上不同的侧链。本文报道的人工跨膜蛋白是具有特定生物活性的最简单的已知蛋白质，仅由起始甲硫氨酸随后是亮氨酸和异亮氨酸的特定序列组成，这两种疏水氨基酸仅在甲基的位置上不同。我们将这些含有亮氨酸（L）和异亮氨酸（I）的蛋白质命名为LIL蛋白质。这些蛋白质在功能上与血小板衍生生长因子β受体的跨膜结构域相互作用，并特异性激活受体以转化细胞。这些蛋白质的完全诱变确定了活性所需的单个氨基酸，并且除了在特定位置的单个异亮氨酸之外，仅由亮氨酸组成的蛋白质转化了细胞。这些令人惊讶的简单蛋白质定义了足以构建具有特定生物活性的蛋白质的最小化学多样性，并改变了我们对细胞环境中活性蛋白质的看法。
We have constructed 26-amino acid transmembrane proteins that specifically transform cells but consist of only two different amino acids. Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains. The artificial transmembrane proteins reported here are the simplest known proteins with specific biological activity, consisting solely of an initiating methionine followed by specific sequences of leucines and isoleucines, two hydrophobic amino acids that differ only by the position of a methyl group. We designate these proteins containing leucine (L) and isoleucine (I) as LIL proteins. These proteins functionally interact with the transmembrane domain of the platelet-derived growth factor beta-receptor and specifically activate the receptor to transform cells. Complete mutagenesis of these proteins identified individual amino acids required for activity, and a protein consisting solely of leucines, except for a single isoleucine at a particular position, transformed cells. These surprisingly simple proteins define the minimal chemical diversity sufficient to construct proteins with specific biological activity and change our view of what can constitute an active protein in a cellular context.