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.

"Effect of the mitochondrial surface on protein stability" [with S. Huang and S. Murphy] Proc. Natl. Acad. Sci. USA 97: 12991-12996 (2000).

"Protein unfolding by mitochondria" [with N. Pfanner and W. Voos] EMBO Reports 1 : 404-410 (2000).

"Mitochondria unfold precursor proteins by unraveling them from their N-termini" [with S. Huang, K.S. Ratliff, M.P. Schwartz, and J.M. Spenner] Nature Struct. Biol. 6: 1132-1138 (1999).

"The dimensions of the protein import channels in the outer and inner mitochondrial membranes" [with M.P. Schwartz], Proc. Natl. Acad. Sci. USA 96: 13086-13090 (1999).

"The structure of precursor proteins during import into mitochondria" [with M.P. Swartz and S. Huang], J. Biol. Chem 274: 12759-12764 (1999).

"Active unfolding of precursor proteins during mitochondrial protein import" [with A. Azem, K. Ratliff, B. S. Glick, K. Schmid, and G. Schatz], EMBO J. 16: 6727-6736 (1997).

View all publications by publications by Andreas Matouschek listed in the National Library of Medicine (PubMed).