Sequential Checkpoints Govern Substrate Selection During Cotranslational Protein Targeting

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Science  07 May 2010:
Vol. 328, Issue 5979, pp. 757-760
DOI: 10.1126/science.1186743

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Proper protein localization is essential for all cells. However, the precise mechanism by which high fidelity is achieved is not well understood for any protein-targeting pathway. To address this fundamental question, we investigated the signal recognition particle (SRP) pathway in Escherichia coli, which delivers proteins to the bacterial inner membrane through recognition of signal sequences on cargo proteins. Fidelity was thought to arise from the inability of SRP to bind strongly to incorrect cargos. Using biophysical assays, we found that incorrect cargos were also rejected through a series of checkpoints during subsequent steps of targeting. Thus, high fidelity of substrate selection is achieved through the cumulative effect of multiple checkpoints; this principle may be generally applicable to other pathways involving selective signal recognition.

  • * Present address: Department of Molecular Medicine, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.

  • Present address: WongPartnership LLP, One George Street, No. 20-01, Singapore, 049145.

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