Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER
| Autor: | Yu-Hsien Hwang Fu, Hao-Hsuan Hsieh, Nenad Ban, Daniel Boehringer, Ahmad Jomaa, Sowmya Chandrasekar, Shu-ou Shan, Simone Mattei, SangYoon Chung, Xuemeng Sun, Shimon Weiss, Ruilin Qian, Jae Ho Lee, Xiaotian Bi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Signal recognition particle Multidisciplinary Endoplasmic reticulum Mutant Biophysics Guanosine SciAdv r-articles GTPase macromolecular substances environment and public health Biochemistry Cell biology 03 medical and health sciences chemistry.chemical_compound Cytosol 0302 clinical medicine chemistry Generic health relevance Biological regulation Signal recognition particle receptor 030217 neurology & neurosurgery Research Articles 030304 developmental biology Research Article |
| Zdroj: | Science Advances Science advances, vol 7, iss 21 Science Advances, 7 (21) |
| ISSN: | 2375-2548 |
| Popis: | The conserved signal recognition particle (SRP) cotranslationally delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum (ER). The molecular mechanism by which eukaryotic SRP transitions from cargo recognition in the cytosol to protein translocation at the ER is not understood. Here, structural, biochemical, and single-molecule studies show that this transition requires multiple sequential conformational rearrangements in the targeting complex initiated by guanosine triphosphatase (GTPase)–driven compaction of the SRP receptor (SR). Disruption of these rearrangements, particularly in mutant SRP54G226E linked to severe congenital neutropenia, uncouples the SRP/SR GTPase cycle from protein translocation. Structures of targeting intermediates reveal the molecular basis of early SRP-SR recognition and emphasize the role of eukaryote-specific elements in regulating targeting. Our results provide a molecular model for the structural and functional transitions of SRP throughout the targeting cycle and show that these transitions provide important points for biological regulation that can be perturbed in genetic diseases. Science Advances, 7 (21) ISSN:2375-2548 |
| Databáze: | OpenAIRE |
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