Biochemistry & Molecular Pharmacology
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Amino Acid Motifs; Cathepsin A; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Kinetics; Membrane Transport Proteins; Multiprotein Complexes; Mutagenesis, Site-Directed; Mutation, Missense; Phenotype; Protein Binding; Protein Sorting Signals; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences
The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7, and TM8 in Sec61p) to expose the signal sequence-binding site. To gain mechanistic insight into lateral gate opening, mutations were introduced into a lumenal loop (L7) that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in both the posttranslational and cotranslational translocation pathways due to a kinetic delay in channel gating. The translocation defect caused by L7 mutations could be suppressed by the prl class of sec61 alleles, which reduce the fidelity of signal sequence recognition. The prl mutants are proposed to act by destabilizing the closed conformation of the translocation channel. Our results indicate that the equilibrium between the open and closed conformations of the protein translocation channel maintains a balance between translocation activity and signal sequence recognition fidelity.
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Citation: Mol Biol Cell. 2011 Sep;22(17):2983-93. Epub 2011 Jul 7. Link to article on publisher's website
DOI of Published Version
Molecular biology of the cell
Trueman, Steven F.; Mandon, Elisabet C.; and Gilmore, Reid, "Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity" (2011). GSBS Student Publications. 1766.