Eichmann Cédric, Tzitzilonis Christos, Bordignon Enrica, Maslennikov Innokentiy, Choe Senyon, Riek Roland
From the Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland and.
From the Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland and the Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037.
J Biol Chem. 2014 Aug 22;289(34):23482-503. doi: 10.1074/jbc.M114.571935. Epub 2014 Jun 23.
The solution NMR structure of the α-helical integral membrane protein YgaP from Escherichia coli in mixed 1,2-diheptanoyl-sn-glycerol-3-phosphocholine/1-myristoyl-2-hydroxy-sn-glycero-3-phospho-(1'-rac-glycerol) micelles is presented. In these micelles, YgaP forms a homodimer with the two transmembrane helices being the dimer interface, whereas the N-terminal cytoplasmic domain includes a rhodanese-fold in accordance to its sequence homology to the rhodanese family of sulfurtransferases. The enzymatic sulfur transfer activity of full-length YgaP as well as of the N-terminal rhodanese domain only was investigated performing a series of titrations with sodium thiosulfate and potassium cyanide monitored by NMR and EPR. The data indicate the thiosulfate concentration-dependent addition of several sulfur atoms to the catalytic Cys-63, which process can be reversed by the addition of potassium cyanide. The catalytic reaction induces thereby conformational changes within the rhodanese domain, as well as on the transmembrane α-helices of YgaP. These results provide insights into a potential mechanism of YgaP during the catalytic thiosulfate activity in vivo.
本文展示了来自大肠杆菌的α-螺旋整合膜蛋白YgaP在1,2-二庚酰-sn-甘油-3-磷酸胆碱/1-肉豆蔻酰-2-羟基-sn-甘油-3-磷酸-(1'-rac-甘油)混合胶束中的溶液核磁共振结构。在这些胶束中,YgaP形成同二聚体,两个跨膜螺旋构成二聚体界面,而N端胞质结构域根据其与硫转移酶罗丹明家族的序列同源性包含一个罗丹明折叠。通过用硫代硫酸钠和氰化钾进行一系列滴定,并由核磁共振和电子顺磁共振监测,研究了全长YgaP以及仅N端罗丹明结构域的酶促硫转移活性。数据表明硫代硫酸盐浓度依赖性地向催化性半胱氨酸-63添加多个硫原子,该过程可通过添加氰化钾逆转。催化反应由此诱导罗丹明结构域内以及YgaP跨膜α-螺旋上的构象变化。这些结果为YgaP在体内催化硫代硫酸盐活性期间的潜在机制提供了见解。