Membrane targeting signals of the bacterial SRP system

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The signal recognition particle of Escherichia coli consists of a 48-kDa protein Ffh and a 4.5S RNA. Membrane proteins that have uncleavable signal sequences are recognized as substrates, are targeted to the membrane and are released after contacting the SRP receptor protein FtsY. We recently found that the Sec/YidC-independent membrane sensor protein KdpD is targeted by SRP and a KdpD-GFP fusion protein localizes at the membrane depending on the presence of Ffh or FtsY, respectively. In addition, the KdpD protein is not inserted into the membrane in strains that are deficient for Ffh or FtsY. The information within the KdpD protein that confers SRP interaction was found in the amino-terminal cytoplasmic domain of KdpD in the residues 22-48. Further experiments suggest that this sequence is sufficient to bind to SRP and to direct GFP to the membrane. We now want to analyse to which region of SRP the signal binds and determine the relevant sequence specificity. Co-crystallization with SRP should give the molecular details of the interaction. Sequence comparisons with other membrane proteins should answer whether such signals are ubiquitous for membrane proteins that have large amino-terminal hydrophilic regions. Another aspect we want to address is the question how the decision for the SRP-targeted protein is made to be either directed to the Sec translocase, to the YidC membrane insertase or straight to the bilayer. An interesting possibility is that the signal for each of the targets is different and specifies the interaction with SecYEG, YidC or directly with the bilayer.