Journal Article

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

Chandrasekar, Sowmya, Shan, Shu-ou, Ban, Nenad, Kobayashi, Kan, Jomaa, Ahmad, Lee, Jae Ho, Boehringer, Daniel

2018

Overview

Ribosomes synthesizing membrane or secretory proteins are targeted to the endoplasmic reticulum (ER) in eukaryotic cells by the signal recognition particle (SRP). Upon reaching the ER, the SRP interacts with its receptor to promote transfer of the signal sequence to the protein-conducting channel or translocon. Kobayashi et al. studied the ribosomal complex that forms on the ER, in which the SRP and its receptor interact to transfer the newly synthesized protein to the translocon. The observed organization of the assembly reveals the roles of multiple eukaryotic-specific protein components present in the SRP and its receptor in stabilizing the conformation that facilitates signal sequence handover. Science , this issue p. 323 Eukaryotic-specific signal recognition particle and receptor components stabilize the ribosomal endoplasmic reticulum–targeting complex. 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–electron microscopy 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 guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.

• Publisher: The American Association for the Advancement of Science
• Subject: Amino acid sequence / Animals / Assembly / Cryoelectron Microscopy / Electron microscopy / Endoplasmic reticulum / GTP Phosphohydrolases - chemistry / Guanosine / Guanosine Triphosphate - chemistry / Hydrolysis / Mammals / Protein Conformation / Protein Multimerization / Protein Sorting Signals / Proteins / Receptors, Cytoplasmic and Nuclear - chemistry / Receptors, Cytoplasmic and Nuclear - ultrastructure / Receptors, Peptide - chemistry / Receptors, Peptide - ultrastructure / Ribonucleic acid / Ribosomal DNA / Ribosomes / Ribosomes - chemistry / Ribosomes - ultrastructure / RNA / RNA - chemistry / Signal recognition particle / Synthesis / Target recognition / Translocation / Windows (intervals)