Sec translocase nanomachine dynamics (STraND)

At the molecular level, all of biology is essentially a series of chemical reactions invariably catalyzed by protein molecules. Proteins carry out their highly specialized functions through a series of coordinated motions (dynamics) and interactions with other biological molecules. StraND seeks to understand how protein dynamics directly correlates with protein function in bacterial protein secretion by the Sec Translocase system. The Sec translocase is a complex cellular machine that facilitates protein sorting and export across the bacterial membrane. Protein secretion is a universally important process, and the molecules that make up the Sec translocase are evolutionarily conserved across all of biology. The ultimate aim of this project is to piece together the various steps in protein translocation by understanding the different motions that Sec translocase makes during its reaction cycle. To this end, STraND will use a battery of biophysical tools such as Structural Mass spectrometry and single molecule FRET spectroscopy (smFRET) coupled to biochemical assays, to dissect each step in the protein translocation pathway. These tools are low resolution but cutting edge tools that when combined would provide deep insights into the functioning of complex protein systems. A mechanistic model will be developed that would be of significant importance overall not only to the field of protein translocation but also to biophysical analysis of membrane proteins at large.