|
|
Line 3: |
Line 3: |
| <SX load='6nd1' size='340' side='right' viewer='molstar' caption='[[6nd1]], [[Resolution|resolution]] 4.10Å' scene=''> | | <SX load='6nd1' size='340' side='right' viewer='molstar' caption='[[6nd1]], [[Resolution|resolution]] 4.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6nd1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ND1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ND1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nd1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ND1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ND1 FirstGlance]. <br> |
- | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6nd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nd1 OCA], [http://pdbe.org/6nd1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nd1 RCSB], [http://www.ebi.ac.uk/pdbsum/6nd1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nd1 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1Å</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nd1 OCA], [https://pdbe.org/6nd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nd1 RCSB], [https://www.ebi.ac.uk/pdbsum/6nd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nd1 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/SEC72_YEAST SEC72_YEAST]] Acts as non-essential component of the Sec62/63 complex which is involved in SRP-independent post-translational translocation across the endoplasmic reticulum (ER) and functions together with the Sec61 complex and KAR2 in a channel-forming translocon complex. A cycle of assembly and disassembly of Sec62/63 complex from SEC61 may govern the activity of the translocon. SEC72 may be involved in signal peptide recognition for a defined subset of leader peptides, or may increase the efficiency of unusual or "difficult" secretory precursors to the translocation pore, it may be that this protein binds charged leader peptides to the membrane until they engage the translocation apparatus. [[http://www.uniprot.org/uniprot/SC6B1_YEAST SC6B1_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. [[http://www.uniprot.org/uniprot/SC61A_YEAST SC61A_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. [[http://www.uniprot.org/uniprot/SC61G_YEAST SC61G_YEAST]] Part of the Sec61 complex, which is the major component of 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. Also part of the Ssh1 complex, which probably is the major component of a channel-forming translocon complex that may function exclusively in the cotranslational pathway of protein ER import.[HAMAP-Rule:MF_00422] [[http://www.uniprot.org/uniprot/SEC63_YEAST SEC63_YEAST]] Acts as component of the Sec62/63 complex which is involved in SRP-independent post-translational translocation across the endoplasmic reticulum (ER) and functions together with the Sec61 complex and KAR2 in a channel-forming translocon complex. A cycle of assembly and disassembly of Sec62/63 complex from SEC61 may govern the activity of the translocon. SEC63 may affect SEC1-polypeptide interactions by increasing the affinity of targeting pathways for SEC61 and/or by modifying SEC61 to allow more efficient polypeptide interaction. May also be involved in SRP-dependent cotranslational translocation. Is essential for cell growth and for germination.<ref>PMID:11226176</ref> [[http://www.uniprot.org/uniprot/SEC66_YEAST SEC66_YEAST]] Acts as component of the Sec62/63 complex which is involved in SRP-independent post-translational translocation across the endoplasmic reticulum (ER) and functions together with the Sec61 complex and KAR2 in a channel-forming translocon complex. A cycle of assembly and disassembly of Sec62/63 complex from SEC61 may govern the activity of the translocon. SEC66 is required to attach or retain SEC72 in the SEC63 complex. It is essential for growth at elevated temperatures. | + | [https://www.uniprot.org/uniprot/SC61G_YEAST SC61G_YEAST] Part of the Sec61 complex, which is the major component of 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. Also part of the Ssh1 complex, which probably is the major component of a channel-forming translocon complex that may function exclusively in the cotranslational pathway of protein ER import.[HAMAP-Rule:MF_00422] |
- | <div style="background-color:#fffaf0;">
| + | |
- | == Publication Abstract from PubMed ==
| + | |
- | Many proteins must translocate through the protein-conducting Sec61 channel in the eukaryotic endoplasmic reticulum membrane or the SecY channel in the prokaryotic plasma membrane(1,2). Proteins with hydrophobic signal sequences are first recognized by the signal recognition particle (SRP)(3,4) and then moved co-translationally through the Sec61/SecY channel by the associated translating ribosome. Substrates with less hydrophobic signal sequences bypass SRP and are moved through the channel post-translationally(5,6). In eukaryotic cells, post-translational translocation is mediated by the association of the Sec61 channel with another membrane protein complex, the Sec62/Sec63 complex(7-9), and substrates are moved through the channel by the luminal BiP ATPase(9). How the Sec62/63 complex activates the Sec61 channel for post-translational translocation is unclear. Here, we report the electron cryo-microscopy (cryo-EM) structure of the Sec complex from S. cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71, and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting with both cytosolic loops in the C-terminal half of Sec61 and trans-membrane (TM) segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp70 (ref. (10)). Our structure shows how the Sec61 channel is activated for post-translational protein translocation.
| + | |
- | | + | |
- | Structure of the post-translational protein translocation machinery of the ER membrane.,Wu X, Cabanos C, Rapoport TA Nature. 2018 Dec 31. pii: 10.1038/s41586-018-0856-x. doi:, 10.1038/s41586-018-0856-x. PMID:30644436<ref>PMID:30644436</ref>
| + | |
- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
- | </div>
| + | |
- | <div class="pdbe-citations 6nd1" style="background-color:#fffaf0;"></div>
| + | |
- | == References ==
| + | |
- | <references/>
| + | |
| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
- | [[Category: Atcc 18824]] | |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
- | [[Category: Cabanos, C]] | + | [[Category: Cabanos C]] |
- | [[Category: Rapoport, T A]] | + | [[Category: Rapoport TA]] |
- | [[Category: Wu, X]] | + | [[Category: Wu X]] |
- | [[Category: Post-translational translocation]]
| + | |
- | [[Category: Protein transport]]
| + | |
- | [[Category: Sec61]]
| + | |
- | [[Category: Sec63]]
| + | |
- | [[Category: Transport protein]]
| + | |
- | [[Category: Yeast]]
| + | |