Tanaka Koji, Caaveiro Jose M M, Tsumoto Kouhei
Department of Chemistry and Biotechnology and ‡Department of Bioengineering, School of Engineering, The University of Tokyo , Bunkyo-ku, Tokyo 113-8656, Japan.
Biochemistry. 2015 Nov 24;54(46):6863-6. doi: 10.1021/acs.biochem.5b01112. Epub 2015 Nov 11.
The bidirectional transformation of a protein between its native water-soluble and integral transmembrane conformations is demonstrated for FraC, a hemolytic protein of the family of pore-forming toxins. In the presence of biological membranes, the water-soluble conformation of FraC undergoes a remarkable structural reorganization generating cytolytic transmembrane nanopores conducive to cell death. So far, the reverse transformation from the native transmembrane conformation to the native water-soluble conformation has not been reported. We describe the use of detergents with different physicochemical properties to achieve the spontaneous conversion of transmembrane pores of FraC back into the initial water-soluble state. Thermodynamic and kinetic stability data suggest that specific detergents cause an asymmetric change in the energy landscape of the protein, allowing the bidirectional transformation of a membrane protein.
形成孔道毒素家族的溶血蛋白FraC展现出了蛋白质在其天然水溶性构象和完整跨膜构象之间的双向转变。在生物膜存在的情况下，FraC的水溶性构象会经历显著的结构重组，产生有利于细胞死亡的溶细胞跨膜纳米孔。到目前为止，从天然跨膜构象到天然水溶性构象的逆向转变尚未见报道。我们描述了使用具有不同物理化学性质的去污剂来实现FraC跨膜孔自发转化回初始水溶性状态的过程。热力学和动力学稳定性数据表明，特定的去污剂会导致蛋白质能量景观的不对称变化，从而实现膜蛋白的双向转变。
