Mitochondria unfold precursor proteins by unraveling them from their N-termini.
Protein unfolding is a key step in the life cycle of many proteins, including certain proteins that are degraded by ATP-dependent proteases or translocated across membranes. The detailed mechanisms of these unfolding processes are not understood. Precursor proteins are unfolded and imported into mitochondria by a macromolecular machine that spans two membranes and contains at least nine different proteins. Here we examine import of a model precursor protein derived from the ribonuclease barnase and show that mitochondria unfold this protein by unraveling it from its N-terminus. Because barnase in free-solution unfolds by a different pathway, our results demonstrate that mitochondria catalyze unfolding in the way that enzymes catalyze reactions, namely by changing reaction pathways. The effectiveness of this mechanism depends on the structure of the N-terminal part of the precursor protein.
Huang
S
S
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Ratliff
K S
KS
Schwartz
M P
MP
Spenner
J M
JM
Matouschek
A
A
D000818:Animals; D001426:Bacterial Proteins; D001692:Biological Transport; D003545:Cysteine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004795:Enzyme Stability; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012996:Solutions; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D004220:Disulfides; D008024:Ligands; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D012996:Solutions; D013762:Tetrahydrofolate Dehydrogenase; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D003545:Cysteine