Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity
| Autor: | Reid Gilmore, Steven F. Trueman, Elisabet C. Mandon |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Signal peptide
Sec61 Saccharomyces cerevisiae Proteins Biosynthesis and Biodegradation Amino Acid Motifs Mutation Missense Cathepsin A Chromosomal translocation Saccharomyces cerevisiae Plasma protein binding Protein Sorting Signals Biology 03 medical and health sciences 0302 clinical medicine Binding site Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Molecular Biology 030304 developmental biology 0303 health sciences digestive oral and skin physiology Membrane Transport Proteins Articles Cell Biology Translocon Protein Structure Tertiary Transport protein Kinetics Protein Transport Phenotype Biochemistry Multiprotein Complexes Mutagenesis Site-Directed Biophysics SEC Translocation Channels 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e11-01-0070 |
| Popis: | The transition between the closed and open conformations of the protein translocation channel controls the efficiency of protein translocation and the fidelity of signal sequence recognition. Mutations in Sec61 that delay or accelerate this structural transition have antagonistic effects on translocation efficiency and fidelity. 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. |
| Databáze: | OpenAIRE |
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