Faculty
Andreas Matouschek, PhD
Professor
Biochemistry Molecular Biology, and Cell Biology
PhD, Cambridge
Email: matouschek@northwestern.edu
Phone: (847) 467-3570
Fax: (847) 467-1380
Room: Pancoe Rm 4105
Research Interests
Mechanisms of Macromolecular Machines
To be active most proteins must fold into well-defined three-dimensional structures. However, regulated unfolding is also critically important during the life cycle of many proteins, including proteins that are translocated across membranes and proteins that are degraded by ATP-dependent proteases.
Some of these unfolding processes show surprising similarities. For instance, many proteins are targeted for unfolding by N- or C-terminal signal sequences and often translational movement of the substrate protein occurs with unfolding. Despite the obvious biological relevance and in contrast to protein folding, protein unfolding in vivo has not been studied.
My laboratory studies the mechanism by which proteins are unfolded by translocases and proteases. We have shown that mitochondria and proteases unfold proteins by unraveling them from their targeting signals. We are now pursuing three trains of investigation: 1) we will identify the components of the mitochondrial import machinery that unravel the protein during import using the methods of yeast cell biology and biochemistry; 2) we will determine the properties of the import motor using biophysical techniques; 3) we will investigate how the ability of a protein to be unfolded by ATP-dependent proteases depends on its three-dimensional structure and how the partial degradation of transcription factors by the proteasome is regulated.
Selected Publications
Targeting proteins for degradation. Schrader EK, Harstad KG, Matouschek A. Nat Chem Biol. 2009 Nov;5(11):815-22.
ATP-dependent proteases differ substantially in their ability to unfold globular proteins. Koodathingal P, Jaffe NE, Kraut DA, Prakash S, Fishbain S, Herman C, Matouschek A. J Biol Chem. 2009 Jul 10;284(28):18674-84. Epub 2009 Apr 21.
Substrate selection by the proteasome during degradation of protein complexes. Prakash S, Inobe T, Hatch AJ, Matouschek A. Nat Chem Biol. 2009 Jan;5(1):29-36. Epub 2008 Nov 23.
How to pick a protein and pull at it. Inobe T, Kraut DA, Matouschek A. Nat Struct Mol Biol. 2008 Nov;15(11):1135-6. No abstract available.
Controlling a single protein in a nanopore through electrostatic traps. Mohammad MM, Prakash S, Matouschek A, Movileanu L. J Am Chem Soc. 2008 Mar 26;130(12):4081-8. Epub 2008 Mar 6.
Protein targeting to ATP-dependent proteases. Inobe T, Matouschek A. Curr Opin Struct Biol. 2008 Feb;18(1):43-51. Epub 2008 Feb 13. Review.
To degrade or release: ubiquitin-chain remodeling. Kraut DA, Prakash S, Matouschek A. Trends Cell Biol. 2007 Sep;17(9):419-21. Epub 2007 Sep 27.
Where to start and when to stop. Tian L, Matouschek A. Nat Struct Mol Biol. 2006 Aug;13(8):668-70. No abstract available. Erratum in: Nat Struct Mol Biol. 2006 Sep;13(9):855.
A conserved processing mechanism regulates the activity of transcription factors Cubitus interruptus and NF-kappaB. Tian L, Holmgren RA, Matouschek A. Nat Struct Mol Biol. 2005 Dec;12(12):1045-53. Epub 2005 Nov 20.
View all publications by Andreas Matouschek listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue