Structure of the quaternary complex between SRP, SR, and translocon bound to the translating ribosome

Nature Communications
Ahmad JomaaNenad Ban

Abstract

During co-translational protein targeting, the signal recognition particle (SRP) binds to the translating ribosome displaying the signal sequence to deliver it to the SRP receptor (SR) on the membrane, where the signal peptide is transferred to the translocon. Using electron cryo-microscopy, we have determined the structure of a quaternary complex of the translating Escherichia coli ribosome, the SRP-SR in the 'activated' state and the translocon. Our structure, supported by biochemical experiments, reveals that the SRP RNA adopts a kinked and untwisted conformation to allow repositioning of the 'activated' SRP-SR complex on the ribosome. In addition, we observe the translocon positioned through interactions with the SR in the vicinity of the ribosome exit tunnel where the signal sequence is extending beyond its hydrophobic binding groove of the SRP M domain towards the translocon. Our study provides new insights into the mechanism of signal sequence transfer from the SRP to the translocon.

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Citations

Nov 18, 2017·Nucleic Acids Research·Evan MercierWolfgang Wintermeyer
Aug 14, 2019·Biological Chemistry·Klemens WildIrmgard Sinning
May 28, 2020·ELife·John P O'DonnellRamanujan S Hegde
Oct 2, 2019·Nature Structural & Molecular Biology·Shuai WangShu-Ou Shan
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Mar 9, 2021·PLoS Computational Biology·A J Harris, Aaron David Goldman
Mar 22, 2021·The Journal of Biological Chemistry·Eric Westhof, Neocles B Leontis
Apr 19, 2021·Trends in Cell Biology·Madeline M DavisBarry D Bruce
May 4, 2021·Frontiers in Molecular Biosciences·Julia OswaldHans-Georg Koch
May 1, 2021·Frontiers in Molecular Biosciences·Chen JiangDamon Huber
Jul 3, 2021·International Journal of Molecular Sciences·Morgana K KelloggAndrey L Karamyshev
Apr 14, 2018·Chemical Reviews·Nicholas J BarrowsMariano A Garcia-Blanco
Mar 30, 2021·The FEBS Journal·Ruth Steinberg, Hans-Georg Koch

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Datasets Mentioned

BETA
EMD-3617

Methods Mentioned

BETA
GTPase
GTPases
X-ray
electrophoresis

Software Mentioned

EPU
PHENIX
CTFFIND3
PyMOL Molecular Graphics System
RELION
ResMap
COOT
DOSEFGPU DRIFTCORR
EMAN
PyMOL

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