title: Sequential checkpoints govern substrate selection during cotranslational protein targeting.
abstract: 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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Rumana
authors.initials: R
authors.lastname: Rashid
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Shu-ou
authors.initials: SO
authors.lastname: Shan
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006160:Guanosine Triphosphate / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008954:Models, Biological; D011485:Protein Binding; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D021381:Protein Transport; D012270:Ribosomes / Q000378:metabolism; D018271:Signal Recognition Particle / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D021382:Protein Sorting Signals; D018271:Signal Recognition Particle; D006160:Guanosine Triphosphate
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