Science, Technology and Engineering

Dougan & Truscott Laboratory

Department of Biochemistry

Research - Regulated Proteolysis

We are interested in a group of proteins referred to as AAA+ proteases that are responsible for general (protein quality control) and regulated protein turn over in bacteria and in some organelles of eukaryotes such as mitochondria. Together with their associated protein cofactors (adaptors) these molecular machines have an intrinsic ability to shape the proteome of their respective compartments thus contributing to key cellular events by controlling the stability of other proteins (substrates). Our research is directed toward gaining an understanding of the molecular mechanism of the AAA+ proteases, substrate delivery by adaptors and the identification of recognition motifs in protein substrates. A detailed understanding of this machinery will allow us to determine the contribution of regulated proteolysis to the temporal and spatial control of important cellular or organellar processes.

AAA+ proteolytic machines	Adaptor-mediated delivery	Substrate recognition

Recent research highlights in this field

• Erbse A., Schmidt R., Bornemann T., Schneider-Mergener J., Mogk A., Zahn R., DOUGAN D.A., Bukau B. (2006). ClpS, is an essential component of the N-end rule pathway in Escherichia coli. Nature 439, 753-756.
• McGrath P.T., Iniesta A.A., Ryan K.R., Shapiro L., McAdams H.H. (2006). A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator. Cell 124, 535-47.
• Kirstein J, Schlothauer T, DOUGAN DA, Lilie H, Tischendorf G, Mogk A, Bukau B, Turgay K. (2006). Adaptor protein controlled oligomerization activates the AAA+ protein ClpC. EMBO J. 25, 1481-91.
• Hinnerwisch J., Fenton W.A., Furtak K.J., Farr G.W., Horwich A.L. (2005) Loops in the central channel of ClpA chaperone mediate protein binding, unfolding, and translocation. Cell 121, 1029-41.
• Martin A., Baker T.A., Sauer R.T. (2005) Rebuilt AAA+ motors reveal operating principles for ATP-fuelled machines. Nature. 437, 1115-20.
• Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. (2005). The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell 123, 277-89.