The mechanism of cotranslational targeting by the “posttranslational” branch of the Sec pathway by SecA.
I am interested in understanding how newly synthesized proteins are recognized and transported across the cytoplasmic membrane by the Sec pathway in bacteria. The central component of this pathway is an integral membrane protein complex, SecYEG, which forms a channel in the cytoplasmic membrane through which substrate proteins are transported. There are two main branches of the Sec pathway by which substrate proteins are delivered to SecYEG: the posttranslational branch and the cotranslational branch. The posttranslational branch is responsible for the export of the majority of soluble periplasmic and outer membrane proteins in E. coli. However, until recently very little was known about how substrate proteins were recognized by the posttranslational branch. Export of substrates of the posttranslational branch typically begins either very late in the process of protein synthesis or after synthesis is complete, which has led to the widespread assumption that substrate recognition is independent of protein synthesis. (In contrast, substrates of the cotranslational branch are recognized very early in translation by the SRP, and the ribosome is directly coupled to SecYEG.) However, I recently discovered that a component of the posttranslational Sec machinery, the ATPase SecA, binds to the ribosome and appears to play a role in cotranslationally channeling proteins into the “posttranslational” translocation pathway.
PhD students in my lab will use current biochemical and bacterial genetics techniques to investigate the details of the molecular mechanism of cotranslational substrate recognition by SecA. Aspects of this mechanism that are of particular interest are the kinetics of association and dissociation of the different intermediates in the targeting pathway, the determinants and underlying mechanism of substrate specificity, and structure-function characterization of the SecA-ribosome complex.
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Huber D, Rajagopalan N, Preissler S, Rocco MA, Merz F, Kramer G, and Bukau B. (2011) SecA interacts with ribosomes in order to facilitate posttranslational translocation in bacteria. Mol Cell. 41:343-53
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