Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, 77030, USA.
Wolfe Laboratories Inc., 19 Presidential Way, Woburn, MA, 01801, USA.
Nat Commun. 2017 Dec 19;8(1):2203. doi: 10.1038/s41467-017-02397-0.
The diverse lipid environment of the biological membrane can modulate the structure and function of membrane proteins. However, little is known about the role that lipids play in modulating protein-protein interactions. Here we employed native mass spectrometry (MS) to determine how individual lipid-binding events to the ammonia channel (AmtB) modulate its interaction with the regulatory protein, GlnK. The thermodynamic signature of AmtB-GlnK in the absence of lipids indicates conformational dynamics. A small number of lipids bound to AmtB is sufficient to modulate the interaction with GlnK, and lipids with different headgroups display a range of allosteric modulation. We also find that lipid chain length and stereochemistry can affect the degree of allosteric modulation, indicating an unforeseen selectivity of membrane proteins toward the chemistry of lipid tails. These results demonstrate that individual lipid-binding events can allosterically modulate the interactions of integral membrane and soluble proteins.
生物膜中多样化的脂质环境可以调节膜蛋白的结构和功能。然而，人们对于脂质在调节蛋白-蛋白相互作用中所起的作用知之甚少。在这里，我们采用了天然质谱（MS）来确定氨通道（AmtB）与单个脂质结合事件如何调节其与调节蛋白 GlnK 的相互作用。在没有脂质的情况下，AmtB-GlnK 的热力学特征表明其构象动力学。少量与 AmtB 结合的脂质足以调节与 GlnK 的相互作用，并且具有不同头基的脂质显示出一系列变构调节。我们还发现脂质链长和立体化学可以影响变构调节的程度，这表明膜蛋白对脂质尾部化学性质的选择性具有意想不到的选择性。这些结果表明，单个脂质结合事件可以变构调节完整膜和可溶性蛋白的相互作用。
