How does Sec63 affect the conformation of Sec61 in yeast?
The Sec complex catalyzes the translocation of proteins of the secretory pathway into the endoplasmic reticulum and the integration of membrane proteins into the endoplasmic reticulum membrane. Some substrate peptides require the presence and involvement of accessory proteins such as Sec63. Recently...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008855&type=printable |
| _version_ | 1826554842476183552 |
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| author | Pratiti Bhadra Lalitha Yadhanapudi Karin Römisch Volkhard Helms |
| author_facet | Pratiti Bhadra Lalitha Yadhanapudi Karin Römisch Volkhard Helms |
| author_sort | Pratiti Bhadra |
| collection | DOAJ |
| description | The Sec complex catalyzes the translocation of proteins of the secretory pathway into the endoplasmic reticulum and the integration of membrane proteins into the endoplasmic reticulum membrane. Some substrate peptides require the presence and involvement of accessory proteins such as Sec63. Recently, a structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins was determined by cryo-electron microscopy (cryo-EM). Here, we show by co-precipitation that the Sec61 channel subunit Sbh1 is not required for formation of stable Sec63-Sec61 contacts. Molecular dynamics simulations started from the cryo-EM conformation of Sec61 bound to Sec63 and of unbound Sec61 revealed how Sec63 affects the conformation of Sec61 lateral gate, plug, pore region and pore ring diameter via three intermolecular contact regions. Molecular docking of SRP-dependent vs. SRP-independent signal peptide chains into the Sec61 channel showed that the pore regions affected by presence/absence of Sec63 play a crucial role in positioning the signal anchors of SRP-dependent substrates nearby the lateral gate. |
| first_indexed | 2024-12-21T04:13:47Z |
| format | Article |
| id | doaj.art-dbc6db1cf96144b5b94adbe37f88e0ce |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2025-03-14T07:47:20Z |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-dbc6db1cf96144b5b94adbe37f88e0ce2025-03-03T05:31:33ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-03-01173e100885510.1371/journal.pcbi.1008855How does Sec63 affect the conformation of Sec61 in yeast?Pratiti BhadraLalitha YadhanapudiKarin RömischVolkhard HelmsThe Sec complex catalyzes the translocation of proteins of the secretory pathway into the endoplasmic reticulum and the integration of membrane proteins into the endoplasmic reticulum membrane. Some substrate peptides require the presence and involvement of accessory proteins such as Sec63. Recently, a structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins was determined by cryo-electron microscopy (cryo-EM). Here, we show by co-precipitation that the Sec61 channel subunit Sbh1 is not required for formation of stable Sec63-Sec61 contacts. Molecular dynamics simulations started from the cryo-EM conformation of Sec61 bound to Sec63 and of unbound Sec61 revealed how Sec63 affects the conformation of Sec61 lateral gate, plug, pore region and pore ring diameter via three intermolecular contact regions. Molecular docking of SRP-dependent vs. SRP-independent signal peptide chains into the Sec61 channel showed that the pore regions affected by presence/absence of Sec63 play a crucial role in positioning the signal anchors of SRP-dependent substrates nearby the lateral gate.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008855&type=printable |
| spellingShingle | Pratiti Bhadra Lalitha Yadhanapudi Karin Römisch Volkhard Helms How does Sec63 affect the conformation of Sec61 in yeast? PLoS Computational Biology |
| title | How does Sec63 affect the conformation of Sec61 in yeast? |
| title_full | How does Sec63 affect the conformation of Sec61 in yeast? |
| title_fullStr | How does Sec63 affect the conformation of Sec61 in yeast? |
| title_full_unstemmed | How does Sec63 affect the conformation of Sec61 in yeast? |
| title_short | How does Sec63 affect the conformation of Sec61 in yeast? |
| title_sort | how does sec63 affect the conformation of sec61 in yeast |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008855&type=printable |
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