Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration.
We present a coarse-grained simulation model that is capable of simulating the minute-timescale dynamics of protein translocation and membrane integration via the Sec translocon, while retaining sufficient chemical and structural detail to capture many of the sequence-specific interactions that driv...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5381951?pdf=render |
| _version_ | 1811268657632772096 |
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| author | Michiel J M Niesen Connie Y Wang Reid C Van Lehn Thomas F Miller |
| author_facet | Michiel J M Niesen Connie Y Wang Reid C Van Lehn Thomas F Miller |
| author_sort | Michiel J M Niesen |
| collection | DOAJ |
| description | We present a coarse-grained simulation model that is capable of simulating the minute-timescale dynamics of protein translocation and membrane integration via the Sec translocon, while retaining sufficient chemical and structural detail to capture many of the sequence-specific interactions that drive these processes. The model includes accurate geometric representations of the ribosome and Sec translocon, obtained directly from experimental structures, and interactions parameterized from nearly 200 μs of residue-based coarse-grained molecular dynamics simulations. A protocol for mapping amino-acid sequences to coarse-grained beads enables the direct simulation of trajectories for the co-translational insertion of arbitrary polypeptide sequences into the Sec translocon. The model reproduces experimentally observed features of membrane protein integration, including the efficiency with which polypeptide domains integrate into the membrane, the variation in integration efficiency upon single amino-acid mutations, and the orientation of transmembrane domains. The central advantage of the model is that it connects sequence-level protein features to biological observables and timescales, enabling direct simulation for the mechanistic analysis of co-translational integration and for the engineering of membrane proteins with enhanced membrane integration efficiency. |
| first_indexed | 2024-04-12T21:26:46Z |
| format | Article |
| id | doaj.art-7da32171d5524cd2834cd436261ca3af |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-12T21:26:46Z |
| publishDate | 2017-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-7da32171d5524cd2834cd436261ca3af2022-12-22T03:16:08ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-03-01133e100542710.1371/journal.pcbi.1005427Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration.Michiel J M NiesenConnie Y WangReid C Van LehnThomas F MillerWe present a coarse-grained simulation model that is capable of simulating the minute-timescale dynamics of protein translocation and membrane integration via the Sec translocon, while retaining sufficient chemical and structural detail to capture many of the sequence-specific interactions that drive these processes. The model includes accurate geometric representations of the ribosome and Sec translocon, obtained directly from experimental structures, and interactions parameterized from nearly 200 μs of residue-based coarse-grained molecular dynamics simulations. A protocol for mapping amino-acid sequences to coarse-grained beads enables the direct simulation of trajectories for the co-translational insertion of arbitrary polypeptide sequences into the Sec translocon. The model reproduces experimentally observed features of membrane protein integration, including the efficiency with which polypeptide domains integrate into the membrane, the variation in integration efficiency upon single amino-acid mutations, and the orientation of transmembrane domains. The central advantage of the model is that it connects sequence-level protein features to biological observables and timescales, enabling direct simulation for the mechanistic analysis of co-translational integration and for the engineering of membrane proteins with enhanced membrane integration efficiency.http://europepmc.org/articles/PMC5381951?pdf=render |
| spellingShingle | Michiel J M Niesen Connie Y Wang Reid C Van Lehn Thomas F Miller Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration. PLoS Computational Biology |
| title | Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration. |
| title_full | Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration. |
| title_fullStr | Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration. |
| title_full_unstemmed | Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration. |
| title_short | Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration. |
| title_sort | structurally detailed coarse grained model for sec facilitated co translational protein translocation and membrane integration |
| url | http://europepmc.org/articles/PMC5381951?pdf=render |
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