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

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Science  22 Mar 2018:
eaar7924
DOI: 10.1126/science.aar7924

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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.

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