School of Chemistry, University of Birmingham, Edgbaston, B15 2TT, UK.
School of Biosciences, University of Birmingham, Edgbaston, B15 2TT, UK.
Angew Chem Int Ed Engl. 2021 Nov 8;60(46):24473-24477. doi: 10.1002/anie.202110500. Epub 2021 Oct 7.
Herein we report unprecedented location-dependent, size-selective binding to designed lanthanide (Ln ) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln selectivity for moderately large Ln ions (Nd to Tb), for the first time we demonstrate that selectivity can be location-dependent and can be programmed into the sequence. A 1 nm linear translation of the binding site towards the N-terminus can convert a selective site into a highly promiscuous one. An X-ray crystal structure, the first of a lanthanide binding site within a coiled coil to be reported, coupled with CD studies, reveal the existence of an optimal radius that likely stems from the structural constraints of the coiled coil scaffold. To the best of our knowledge this is the first report of location-dependent metal selectivity within a coiled coil scaffold, as well as the first report of location-dependent Ln selectivity within a protein.
在此，我们报告了前所未有的、依赖于位置的、对设计的镧系元素（Ln）位点的尺寸选择性结合，这些位点位于微型蛋白质卷曲螺旋支架内。这些工程化的位点不仅对中等大小的 Ln 离子（Nd 到 Tb）表现出不寻常的 Ln 选择性，而且我们首次证明，选择性可以是依赖于位置的，并可以编程到序列中。将结合位点向 N 端线性移动 1nm 可以将选择性位点转换为高度混杂的位点。首个报道的卷曲螺旋内镧系元素结合位点的 X 射线晶体结构，结合 CD 研究，揭示了存在一个最佳半径，这可能源于卷曲螺旋支架的结构限制。据我们所知，这是首次在卷曲螺旋支架内报告位置依赖的金属选择性，也是首次在蛋白质内报告位置依赖的 Ln 选择性。
