Liu Jie, Lu Min
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
J Biol Chem. 2002 Dec 13;277(50):48708-13. doi: 10.1074/jbc.M208773200. Epub 2002 Oct 3.
A major challenge in protein folding is to identify and quantify specific structural determinants that allow native proteins to acquire their unique folded structures. Here we report the engineering of a 52-residue protein (Ala-14) that contains exclusively alanine residues at the hydrophobic a and d positions of a natural heptad-repeat sequence. Ala-14 is unfolded under normal solution conditions yet forms a parallel three-stranded alpha-helical coiled coil in crystals. Ala-14 trimers in the solid state associate with each other through the pairing of polar side chains and formation of an extended network of water-mediated hydrogen bonds. In contrast to the classical view that local intramolecular tertiary interactions dictate the three-dimensional structure of small single-domain proteins, Ala-14 shows that long range intermolecular interactions can be essential in determining the metastable alanine-zipper structure. A similar interplay between short range local and longer range global forces may underlie the conformational properties of the growing class of natively unstructured proteins in biological processes.
蛋白质折叠中的一个主要挑战是识别和量化特定的结构决定因素，这些因素使天然蛋白质能够获得其独特的折叠结构。在此，我们报道了一种52个残基的蛋白质（Ala-14）的工程设计，该蛋白质在天然七肽重复序列的疏水a和d位置仅含有丙氨酸残基。Ala-14在正常溶液条件下是未折叠的，但在晶体中形成平行的三链α-螺旋卷曲螺旋。固态的Ala-14三聚体通过极性侧链的配对和形成水介导的氢键扩展网络而相互关联。与局部分子内三级相互作用决定小单结构域蛋白质三维结构的经典观点相反，Ala-14表明长程分子间相互作用在确定亚稳态丙氨酸拉链结构中可能至关重要。短程局部力和长程全局力之间类似的相互作用可能是生物过程中越来越多的天然无结构蛋白质构象特性的基础。
