Szymańska Aneta, Radulska Adrianna, Czaplewska Paulina, Grubb Anders, Grzonka Zbigniew, Rodziewicz-Motowidło Sylwia
Department of Medicinal Chemistry, Faculty of Chemistry, University of Gdańsk, J. Sobieskiego 18, Gdańsk, Poland.
Acta Biochim Pol. 2009;56(3):455-63. Epub 2009 Jul 27.
Three dimensional domain swapping is one of the mechanisms involved in formation of insoluble aggregates of some amyloidogenic proteins. It has been proposed that proteins able to swap domains may share some common structural elements like conformationally constrained flexible turns/loops. We studied the role of loop L1 in the dimerization of human cystatin C using mutational analysis. Introduction of turn-favoring residues such as Asp or Asn into the loop sequence (in position 57) leads to a significant reduction of the dimer fraction in comparison with the wild type protein. On the other hand, introduction of a proline residue in position 57 leads to efficient dimer formation. Our results confirm the important role of the loop L1 in the dimerization process of human cystatin C and show that this process can be to some extent governed by single amino acid substitution.
三维结构域交换是一些淀粉样蛋白形成不溶性聚集体所涉及的机制之一。有人提出，能够进行结构域交换的蛋白质可能共享一些共同的结构元件，如构象受限的柔性转角/环。我们使用突变分析研究了环L1在人胱抑素C二聚化中的作用。与野生型蛋白相比，在环序列（第57位）中引入有利于转角形成的残基如天冬氨酸或天冬酰胺会导致二聚体比例显著降低。另一方面，在第57位引入脯氨酸残基会导致高效的二聚体形成。我们的结果证实了环L1在人胱抑素C二聚化过程中的重要作用，并表明这一过程在一定程度上可以由单个氨基酸取代来控制。
