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Structure of a Prehandover Mammalian Ribosomal SRP·SRP Receptor Targeting Complex

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Journal Science
Specialty Science
Date 2018 Mar 24
PMID 29567807
Citations 34
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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-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.

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References
1.
Bacher G, Pool M, Dobberstein B . The ribosome regulates the GTPase of the beta-subunit of the signal recognition particle receptor. J Cell Biol. 1999; 146(4):723-30. PMC: 2156146. DOI: 10.1083/jcb.146.4.723. View

2.
Legate K, Falcone D, Andrews D . Nucleotide-dependent binding of the GTPase domain of the signal recognition particle receptor beta-subunit to the alpha-subunit. J Biol Chem. 2000; 275(35):27439-46. DOI: 10.1074/jbc.M003215200. View

3.
Fulga T, Sinning I, Dobberstein B, Pool M . SRbeta coordinates signal sequence release from SRP with ribosome binding to the translocon. EMBO J. 2001; 20(9):2338-47. PMC: 125438. DOI: 10.1093/emboj/20.9.2338. View

4.
Schwartz T, Blobel G . Structural basis for the function of the beta subunit of the eukaryotic signal recognition particle receptor. Cell. 2003; 112(6):793-803. DOI: 10.1016/s0092-8674(03)00161-2. View

5.
Mandon E, Jiang Y, Gilmore R . Dual recognition of the ribosome and the signal recognition particle by the SRP receptor during protein targeting to the endoplasmic reticulum. J Cell Biol. 2003; 162(4):575-85. PMC: 2173783. DOI: 10.1083/jcb.200303143. View