Protein cocrystallization molecules originating from in vitro selected macrocyclic peptides
Protein cocrystallization molecules originating from in vitro selected macrocyclic peptides
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DOI：
10.1016/j.sbi.2014.03.001
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发表时间：
2014-06-01
影响因子：
6.8
通讯作者：
Suga, Hiroaki
中科院分区：
文献类型：
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作者：
Hipolito, Christopher J.;Bashiruddin, Nasir K.;Suga, Hiroaki
跨膜蛋白由于其溶解度低，是难以处理的结晶目标，其大量疏水的外表面必须被包裹在由洗涤剂组成的部分胶束中以避免聚集。不幸的是，在部分胶束内的封装减少了晶格形成所需的特定蛋白质与蛋白质之间的接触。此外，某些跨膜蛋白的高构象灵活性降低了样品的均匀性，从而导致结晶困难。基于抗体支架或其他蛋白性非抗体支架的共结晶配体极大地促进了跨膜蛋白的结晶。最近，体外选择的大环肽配体也显示出促进蛋白质结晶的作用。在这篇综述中，我们讨论了用于发现大环肽配体的选择策略以及转运体PfMATE在体外选择的大环肽复合物中的三维晶体结构。
Transmembrane proteins are intractable crystallization targets due to their low solubility and their substantial hydrophobic outer surfaces must be enclosed within a partial micelle composed of detergents to avoid aggregation. Unfortunately, encapsulation within a partial micelle diminishes specific protein-to-protein contacts needed for crystal lattice formation. In addition, the high conformational flexibility of certain transmembrane proteins reduces sample homogeneity causing difficulty in crystallization. Cocrystallization ligands, based on either antibody scaffolds or other proteinaceous non-antibody scaffolds, have greatly facilitated the crystallization of transmembrane proteins. Recently, in vitro selected macrocyclic peptide ligands have been shown to facilitate protein crystallization as well. In this review, we discuss selection strategies used for the discovery of macrocyclic peptide ligands and the three-dimensional crystal structure of the transporter PfMATE in complex with in vitro selected macrocyclic peptides.