Receptor compaction and GTPase movements drive cotranslational protein translocation
| Autor: | Yu-Hsien Hwang Fu, Shimon Weiss, Jae Ho Lee, SangYoon Chung, Ruilin Qian, Xuemeng Sun, Shu-ou Shan |
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| Rok vydání: | 2020 |
| Předmět: |
Signal peptide
0303 health sciences Signal recognition particle biology Chemistry Endoplasmic reticulum medicine.disease_cause environment and public health Ribosome Cell biology 03 medical and health sciences 0302 clinical medicine Protein targeting biology.protein medicine Translocase Biological regulation Signal recognition particle receptor 030217 neurology & neurosurgery 030304 developmental biology |
| Popis: | Signal recognition particle (SRP) is a universally conserved targeting machine that couples the synthesis of ~30% of the proteome to their proper membrane localization1,2. In eukaryotic cells, SRP recognizes translating ribosomes bearing hydrophobic signal sequences and, through interaction with SRP receptor (SR), delivers them to the Sec61p translocase on the endoplasmic reticulum (ER) membrane1,2. How SRP ensures efficient and productive initiation of protein translocation at the ER is not well understood. Here, single molecule fluorescence spectroscopy demonstrates that cargo-loaded SRP induces a global compaction of SR, driving a >90 Å movement of the SRP•SR GTPase complex from the vicinity of the ribosome exit, where it initially assembles, to the distal site of SRP. These rearrangements bring translating ribosomes near the membrane, expose conserved Sec61p docking sites on the ribosome and weaken SRP’s interaction with the signal sequence on the nascent polypeptide, thus priming the translating ribosome for engaging the translocation machinery. Disruption of these rearrangements severely impairs cotranslational protein translocation and is the cause of failure in an SRP54 mutant linked to severe congenital neutropenia. Our results demonstrate that multiple largescale molecular motions in the SRP•SR complex are required to drive the transition from protein targeting to translocation; these post-targeting rearrangements provide potential new points for biological regulation as well as disease intervention. |
| Databáze: | OpenAIRE |
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