Project Ideas:

We have the crystal structure of NG domain FtsY (apo, 1FTS.pdb) from Irmi's group for E. coli. However, we have no structure of E. coli Ffh. We can use the NG domain Ffh structures from T. aquaticus and A. ambivalens and the E. coli sequence to model an apo NG domain structure from E. coli. Then we can dock GTP-Mg²⁺ to the apo-forms of the NG domain Ffh and FtsY from E. coli and compare these results to the GDP and GMPPNP structures available to compare the conforational changes induced by GTP-binding. With the new coordinates from Freymann's group and those form Walter's group, we can compare the conformational differences between the GMPPNP, GDP, and apo forms of Ffh. We can model a SRP/SR complex where both are GTP-Mg²⁺ bound. We should look at the importance of the four Arg residues at the proposed interface in Ffh and FtsY. Irmi is making mutants of these right now and it will be interesting to compare the results of our modelling and her experimental work. Also, many mutants have been made for the SRP and SR in E. coli and this data can be used to guide our work. There is also a structure for the 5 subunit signal peptidase enzyme (1B12.pdb) with a beta-lactam inhibitor bound. This hydrolase cleaves the signal sequence after the protein is transported through the pore. A comparison should be made between the active site of the signal peptidase and the M-domain of Ffh. (There is a structure for the human and Thermus aquaticus (2FFH.pdb) SRP M domain. Both interact with the signal peptide so there should be similarities between the sites of interaction on both of these proteins. An examination of the signal peptidase site could lead to new insights as to exactly how the SRP M-domain interacts with the signal peptide.