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Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes

Here, we review recent molecular modelling and simulation studies of the Sec translocon, the primary component/channel of protein translocation into the endoplasmic reticulum (ER) and bacterial periplasm, respectively. Our focus is placed on the eukaryotic Sec61, but we also mention modelling studie...

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Detalles Bibliográficos
Autores principales: Bhadra, Pratiti, Helms, Volkhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509349/
https://www.ncbi.nlm.nih.gov/pubmed/34639046
http://dx.doi.org/10.3390/ijms221910705
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author Bhadra, Pratiti
Helms, Volkhard
author_facet Bhadra, Pratiti
Helms, Volkhard
author_sort Bhadra, Pratiti
collection PubMed
description Here, we review recent molecular modelling and simulation studies of the Sec translocon, the primary component/channel of protein translocation into the endoplasmic reticulum (ER) and bacterial periplasm, respectively. Our focus is placed on the eukaryotic Sec61, but we also mention modelling studies on prokaryotic SecY since both systems operate in related ways. Cryo-EM structures are now available for different conformational states of the Sec61 complex, ranging from the idle or closed state over an inhibited state with the inhibitor mycolactone bound near the lateral gate, up to a translocating state with bound substrate peptide in the translocation pore. For all these states, computational studies have addressed the conformational dynamics of the translocon with respect to the pore ring, the plug region, and the lateral gate. Also, molecular simulations are addressing mechanistic issues of insertion into the ER membrane vs. translocation into the ER, how signal-peptides are recognised at all in the translocation pore, and how accessory proteins affect the Sec61 conformation in the co- and post-translational pathways.
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spelling pubmed-85093492021-10-13 Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes Bhadra, Pratiti Helms, Volkhard Int J Mol Sci Review Here, we review recent molecular modelling and simulation studies of the Sec translocon, the primary component/channel of protein translocation into the endoplasmic reticulum (ER) and bacterial periplasm, respectively. Our focus is placed on the eukaryotic Sec61, but we also mention modelling studies on prokaryotic SecY since both systems operate in related ways. Cryo-EM structures are now available for different conformational states of the Sec61 complex, ranging from the idle or closed state over an inhibited state with the inhibitor mycolactone bound near the lateral gate, up to a translocating state with bound substrate peptide in the translocation pore. For all these states, computational studies have addressed the conformational dynamics of the translocon with respect to the pore ring, the plug region, and the lateral gate. Also, molecular simulations are addressing mechanistic issues of insertion into the ER membrane vs. translocation into the ER, how signal-peptides are recognised at all in the translocation pore, and how accessory proteins affect the Sec61 conformation in the co- and post-translational pathways. MDPI 2021-10-02 /pmc/articles/PMC8509349/ /pubmed/34639046 http://dx.doi.org/10.3390/ijms221910705 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bhadra, Pratiti
Helms, Volkhard
Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes
title Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes
title_full Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes
title_fullStr Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes
title_full_unstemmed Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes
title_short Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes
title_sort molecular modeling of signal peptide recognition by eukaryotic sec complexes
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509349/
https://www.ncbi.nlm.nih.gov/pubmed/34639046
http://dx.doi.org/10.3390/ijms221910705
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