7aft | pdb_00007aft
Cryo-EM structure of the signal sequence-engaged post-translational Sec translocon
Structural highlights
FunctionSC61A_YEAST Part of the Sec61 complex, which is the major component of a channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). The functional states of the translocon complex include co- and post-translational ER import, cotranslational membrane protein integration and retrograde transport of misfolded proteins out of the ER. In the cotranslational pathway, ribosomes synthesizing presecretory proteins are targeted to the translocon by the cytosolic signal recognition particle (SRP) and its ER-localized receptor. The association of the Sec61 complex with the ribosome is mediated by the 28S rRNA of the large ribosomal subunit. SRP-independent post-translational translocation requires the association of additional factors, such as the Sec62/63 complex and KAR2. In an initial step, the signal sequence seems to bind simultaneously to SEC61 and SEC62. A cycle of assembly and disassembly of Sec62/63 complex from SEC61 may govern the activity of the translocon. SEC61 mediates the association with the ribosome. Publication Abstract from PubMedIn eukaryotes, most secretory and membrane proteins are targeted by an N-terminal signal sequence to the endoplasmic reticulum, where the trimeric Sec61 complex serves as protein-conducting channel (PCC). In the post-translational mode, fully synthesized proteins are recognized by a specialized channel additionally containing the Sec62, Sec63, Sec71, and Sec72 subunits. Recent structures of this Sec complex in the idle state revealed the overall architecture in a pre-opened state. Here, we present a cryo-EM structure of the yeast Sec complex bound to a substrate, and a crystal structure of the Sec62 cytosolic domain. The signal sequence is inserted into the lateral gate of Sec61alpha similar to previous structures, yet, with the gate adopting an even more open conformation. The signal sequence is flanked by two Sec62 transmembrane helices, the cytoplasmic N-terminal domain of Sec62 is more rigidly positioned, and the plug domain is relocated. We crystallized the Sec62 domain and mapped its interaction with the C-terminus of Sec63. Together, we obtained a near-complete and integrated model of the active Sec complex. Architecture of the active post-translational Sec translocon.,Weng TH, Steinchen W, Beatrix B, Berninghausen O, Becker T, Bange G, Cheng J, Beckmann R EMBO J. 2020 Dec 11:e105643. doi: 10.15252/embj.2020105643. PMID:33305433[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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