Effects of Antibiotics and a Proto-Oncogene Homolog on Destruction of Protein Translocator SecY

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Science  07 Aug 2009:
Vol. 325, Issue 5941, pp. 753-756
DOI: 10.1126/science.1172221

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Jamming Protein Translocation

Antibiotics are tremendously important drugs in modern medicine, yet we are still learning precisely how they work. SecY is a bacterial membrane protein that is part of a complex that allows protein secretion across the membrane. Van Stelten et al. (p. 753; see the Perspective by Breukink) found in Escherichia coli cells that if the protein translocator complex becomes jammed with a protein that cannot pass through, the SecY protein is degraded by the protease FtsH, leading to cell death. Cells could be protected by increasing amounts of an inhibitor of FtsH, the YccA protein. Antibiotics that block protein translation also caused jamming of the SecY machinery and destruction of SecY, thus contributing to cell death.


Protein secretion occurs via translocation by the evolutionarily conserved Sec complex. LacZ hybrid proteins have long been used to study translocation in Escherichia coli. Some LacZ hybrids were thought to block secretion by physically jamming the Sec complex, leading to cell death. We found that jammed Sec complexes caused the degradation of essential translocator components by the protease FtsH. Increasing the amounts or the stability of the membrane protein YccA, a known inhibitor of FtsH, counteracted this destruction. Antibiotics that inhibit translation elongation also jammed the translocator and caused the degradation of translocator components, which may contribute to their effectiveness. Intriguingly, YccA is a functional homolog of the proto-oncogene product Bax Inhibitor-1, which may share a similar mechanism of action in regulating apoptosis upon prolonged secretion stress.

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