Creasey Elizabeth A, Delahay Robin M, Bishop Alexandra A, Shaw Robert K, Kenny Brendan, Knutton Stuart, Frankel Gad
Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College, London SW7 2AZ, UK.
Mol Microbiol. 2003 Jan;47(1):209-21. doi: 10.1046/j.1365-2958.2003.03290.x.
Map is an enteropathogenic Escherichia coli (EPEC) protein that is translocated into eukaryotic cells by a type III secretion system. Although not required for the induction of attaching and effacing (A/E) lesion formation characteristic of EPEC infection, translocated Map is suggested to disrupt mitochondrial membrane potential, which may impact upon subsequent functions of the organelle such as control of cell death. Before secretion, many effector proteins are maintained in the bacterial cytosol by association with a specific chaperone. In EPEC, chaperones have been identified for the effector proteins translocated intimin receptor (Tir) and EspF, and for the translocator proteins EspB and EspD. In this study, we present evidence that the Tir-specific chaperone, CesT, also performs a chaperone function for Map. Using a combination of biochemical approaches, we demonstrate specific interaction between CesT and Map. Similar to other chaperone-effector pairings, binding is apparent at the amino-terminus of Map and is indicated to proceed by a similar mechanism to CesT:Tir interaction. Map secretion from a cesT mutant strain (SE884) is shown to be reduced and, importantly, its translocation from this strain after infection of HEp-2 cells is almost totally abrogated. Although other chaperones are reported to have a bivalent binding specificity, CesT is the first member of its family that chaperones more than one protein for translocation.
Map是一种肠道致病性大肠杆菌(EPEC)蛋白,可通过III型分泌系统转运到真核细胞中。尽管诱导EPEC感染特有的黏附和抹平(A/E)损伤形成并非必需,但转运的Map被认为会破坏线粒体膜电位,这可能会影响该细胞器的后续功能,如细胞死亡控制。在分泌之前,许多效应蛋白通过与特定伴侣蛋白结合而维持在细菌细胞质中。在EPEC中,已鉴定出转运内膜蛋白受体(Tir)和EspF效应蛋白以及转运蛋白EspB和EspD的伴侣蛋白。在本研究中,我们提供证据表明,Tir特异性伴侣蛋白CesT也对Map发挥伴侣蛋白功能。通过结合生化方法,我们证明了CesT与Map之间的特异性相互作用。与其他伴侣蛋白-效应蛋白配对类似,结合在Map的氨基末端明显可见,并且表明其通过与CesT:Tir相互作用类似的机制进行。cesT突变株(SE884)的Map分泌减少,重要的是,在感染HEp-2细胞后,该菌株中Map的转运几乎完全被消除。尽管据报道其他伴侣蛋白具有二价结合特异性,但CesT是其家族中第一个为多种蛋白转运发挥伴侣蛋白作用的成员。