Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY

van Stelten, Johna; Silva, Filo; Belin, Dominique; Silhavy, T. J.

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Title		Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY
Authors		van Stelten, Johna Silva, Filo Belin, Dominique Silhavy, T. J.
Published in		Science. 2009, vol. 325, no. 5941, p. 753-756
Abstract		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.
Keywords		ATP-Dependent Proteases/metabolism — Anti-Bacterial Agents/ pharmacology — Bacterial Outer Membrane Proteins/genetics/metabolism — Chloramphenicol/pharmacology — Escherichia coli/ drug effects/genetics/ metabolism — Escherichia coli Proteins/genetics/ metabolism — Heat-Shock Proteins/genetics/metabolism — Membrane Proteins/genetics/ metabolism — Mutant Proteins/metabolism — Periplasmic Proteins/genetics/metabolism — Porins/genetics/metabolism — Protein Sorting Signals — Protein Transport/drug effects — Receptors, Virus/genetics/metabolism — Recombinant Fusion Proteins/metabolism — Serine Endopeptidases/genetics/metabolism — Tetracycline/pharmacology — beta-Galactosidase/genetics/metabolism
Identifiers		DOI: 10.1126/science.1172221 PMID: 19661432
Full text		Article - Limited access to UNIGE Other version: http://www.sciencemag.org/cgi/reprint/325/5941/753.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Translocation des protéines à travers les membranes (169)
Citation (ISO format)		VAN STELTEN, Johna et al. Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY. In: Science, 2009, vol. 325, n° 5941, p. 753-756. https://archive-ouverte.unige.ch/unige:11612