The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site
The ribosome CAR interaction surface behaves as an extension of the decoding center A site and has H-bond interactions with the +1 codon, which is next in line to enter the A site. Through molecular dynamic simulations, we investigated the codon sequence specificity of this CAR–mRNA interaction and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1417 |
| _version_ | 1797487420310028288 |
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| author | Carol Dalgarno Kristen Scopino Mitsu Raval Clara Nachmanoff Eric D. Sakkas Daniel Krizanc Kelly M. Thayer Michael P. Weir |
| author_facet | Carol Dalgarno Kristen Scopino Mitsu Raval Clara Nachmanoff Eric D. Sakkas Daniel Krizanc Kelly M. Thayer Michael P. Weir |
| author_sort | Carol Dalgarno |
| collection | DOAJ |
| description | The ribosome CAR interaction surface behaves as an extension of the decoding center A site and has H-bond interactions with the +1 codon, which is next in line to enter the A site. Through molecular dynamic simulations, we investigated the codon sequence specificity of this CAR–mRNA interaction and discovered a strong preference for GCN codons, suggesting that there may be a sequence-dependent layer of translational regulation dependent on the CAR interaction surface. Dissection of the CAR–mRNA interaction through nucleotide substitution experiments showed that the first nucleotide of the +1 codon dominates over the second nucleotide position, consistent with an energetically favorable zipper-like activity that emanates from the A site through the CAR–mRNA interface. Moreover, the CAR/+1 codon interaction is affected by the identity of nucleotide 3 of +1 GCN codons, which influences the stacking of G and C. Clustering analysis suggests that the A-site decoding center adopts different neighborhood substates that depend on the identity of the +1 codon. |
| first_indexed | 2024-03-09T23:47:25Z |
| format | Article |
| id | doaj.art-19d40fa59ee2448780df2b064bbaa870 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:47:25Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-19d40fa59ee2448780df2b064bbaa8702023-11-23T16:40:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233141710.3390/ijms23031417The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A SiteCarol Dalgarno0Kristen Scopino1Mitsu Raval2Clara Nachmanoff3Eric D. Sakkas4Daniel Krizanc5Kelly M. Thayer6Michael P. Weir7Department of Biology, Wesleyan University, Middletown, CT 06459, USADepartment of Biology, Wesleyan University, Middletown, CT 06459, USADepartment of Biology, Wesleyan University, Middletown, CT 06459, USADepartment of Biology, Wesleyan University, Middletown, CT 06459, USADepartment of Biology, Wesleyan University, Middletown, CT 06459, USADepartment of Mathematics and Computer Science, Wesleyan University, Middletown, CT 06459, USADepartment of Mathematics and Computer Science, Wesleyan University, Middletown, CT 06459, USADepartment of Biology, Wesleyan University, Middletown, CT 06459, USAThe ribosome CAR interaction surface behaves as an extension of the decoding center A site and has H-bond interactions with the +1 codon, which is next in line to enter the A site. Through molecular dynamic simulations, we investigated the codon sequence specificity of this CAR–mRNA interaction and discovered a strong preference for GCN codons, suggesting that there may be a sequence-dependent layer of translational regulation dependent on the CAR interaction surface. Dissection of the CAR–mRNA interaction through nucleotide substitution experiments showed that the first nucleotide of the +1 codon dominates over the second nucleotide position, consistent with an energetically favorable zipper-like activity that emanates from the A site through the CAR–mRNA interface. Moreover, the CAR/+1 codon interaction is affected by the identity of nucleotide 3 of +1 GCN codons, which influences the stacking of G and C. Clustering analysis suggests that the A-site decoding center adopts different neighborhood substates that depend on the identity of the +1 codon.https://www.mdpi.com/1422-0067/23/3/1417ribosome translocationmolecular dynamicsCAR interaction surfaceA-site decoding centerribosome substates |
| spellingShingle | Carol Dalgarno Kristen Scopino Mitsu Raval Clara Nachmanoff Eric D. Sakkas Daniel Krizanc Kelly M. Thayer Michael P. Weir The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site International Journal of Molecular Sciences ribosome translocation molecular dynamics CAR interaction surface A-site decoding center ribosome substates |
| title | The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site |
| title_full | The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site |
| title_fullStr | The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site |
| title_full_unstemmed | The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site |
| title_short | The CAR–mRNA Interaction Surface Is a Zipper Extension of the Ribosome A Site |
| title_sort | car mrna interaction surface is a zipper extension of the ribosome a site |
| topic | ribosome translocation molecular dynamics CAR interaction surface A-site decoding center ribosome substates |
| url | https://www.mdpi.com/1422-0067/23/3/1417 |
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