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Structure of a prehandover mammalian ribosomal SRP•SRP receptor targeting complex

Kobayashi, Kan and Jomaa, Ahmad and Lee, Jae Ho and Chandrasekar, Sowmya and Boehringer, Daniel and Shan, Shu-ou and Ban, Nenad (2018) Structure of a prehandover mammalian ribosomal SRP•SRP receptor targeting complex. Science, 360 (6386). pp. 323-327. ISSN 0036-8075. PMCID PMC6309883. https://resolver.caltech.edu/CaltechAUTHORS:20180326-131741830

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Abstract

Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo-EM structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the GTP hydrolysis of SRP•SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://dx.doi.org/10.1126/science.aar7924DOIArticle
http://www.sciencemag.org/cgi/content/full/science.aar7924/DC1PublisherSupplementary Materials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309883PubMed CentralArticle
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2018 American Association for the Advancement of Science. Received for publication December 18, 2017. Accepted for publication March 12, 2018. Cryo-EM data was collected at the Scientific Center for Optical and Electron Microscopy at the ETH Zurich (ScopeM). We thank P. Tittmann and A. Scaiola for support with data collection and C. Aylett and M. Itten for support with data processing. We also thank P. Bieri for initial help with microsome preparation and structure model building. We are grateful for M. Leibundgut for the critical comments on our structure model and manuscript. Funding: K.K. was supported by Long-Term Fellowships from Toyobo Biotechnology Foundation and European Molecular Biology Organization (EMBO) (ALTF 660-2015). This study was supported by the Swiss National Science Foundation (SNSF) (grant number 310030B_163478), National Center of Excellence in Research (NCCR) RNA & Disease Program of the SNSF (grant number 51NF40_141735) (to N.B.), NIH grant GM107368, Gordon and Betty Moore Foundation grant GBMF2939, and a fellowship from the Weston Havens Foundation (to S.-o.S.). Author contributions: K.K., A.J., S.-o.S., and N.B. designed the experimental strategy. K.K. prepared samples and grids for the cryo-EM analysis. K.K., A.J., and D.B. collected cryo-EM data. K.K. and A.J. processed data, built the structure model, and refined it. J.H.L. and S.C. prepared samples for the functional assays and performed them. K.K. and A.J. wrote the initial draft of the manuscript, and all authors contributed to the final version. Competing interests: None declared. Data and materials availability: The atomic coordinates have been deposited in the Protein Data Bank (PDB ID: 6FRK). The cryo-EM density map has been deposited in Electron Microscopy Data Bank (EMD-4300).
Funders:
Funding AgencyGrant Number
Toyobo Biotechnology Foundation UNSPECIFIED
European Molecular Biology Organization (EMBO)ALTF 660-2015
Swiss National Science Foundation (SNSF)310030B_163478
Swiss National Science Foundation (SNSF)51NF40_141735
NIHGM107368
Gordon and Betty Moore FoundationGBMF2939
Weston Havens FoundationUNSPECIFIED
Issue or Number:6386
PubMed Central ID:PMC6309883
Record Number:CaltechAUTHORS:20180326-131741830
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180326-131741830
Official Citation:Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex. BY KAN KOBAYASHI, AHMAD JOMAA, JAE HO LEE, SOWMYA CHANDRASEKAR, DANIEL BOEHRINGER, SHU-OU SHAN, NENAD BAN. SCIENCE 20 APR 2018 : 323-327
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:85432
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:26 Mar 2018 20:47
Last Modified:03 Oct 2019 19:31

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