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The role of C-terminal helix in the conformational transition of an arginine binding protein
The thermotoga maritima arginine binding protein (TmArgBP) is a periplasmic binding protein that has a short helix at the C-terminal end (CTH), which is swapped between the two chains. We apply a coarse-grained structure-based model (SBM) and all-atom MD simulation on this protein to understand the...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402392/ https://www.ncbi.nlm.nih.gov/pubmed/36035778 http://dx.doi.org/10.1016/j.yjsbx.2022.100071 |
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author | Santhakumar, Vinothini Manuel Mascarenhas, Nahren |
author_facet | Santhakumar, Vinothini Manuel Mascarenhas, Nahren |
author_sort | Santhakumar, Vinothini |
collection | PubMed |
description | The thermotoga maritima arginine binding protein (TmArgBP) is a periplasmic binding protein that has a short helix at the C-terminal end (CTH), which is swapped between the two chains. We apply a coarse-grained structure-based model (SBM) and all-atom MD simulation on this protein to understand the mechanism and the role of CTH in the conformational transition. When the results of SBM simulations of TmArgBP in the presence and absence of CTH are compared, we find that CTH is strategically located at the back of the binding pocket restraining the open-state conformation thereby disengaging access to the closed-state. We also ran all-atom MD simulations of open-state TmArgBP with and without CTH and discovered that in the absence of CTH the protein could reach the closed-state within 250 ns, while in its presence, the protein remained predominantly in its open-state conformation. In the simulation started from unliganded closed-state conformation without CTH, the protein exhibited multiple transitions between the two states, suggesting CTH as an essential structural element to stabilize the open-state conformation. In another simulation that began with an unliganded closed-state conformation with CTH, the protein was able to access the open-state. In this simulation the CTH was observed to reorient itself to interact with the protein emphasizing its role in assisting the conformational change. Based on our findings, we believe that CTH not only acts as a structural element that constraints the protein in its open-state but it may also guide the protein back to its open-state conformation upon ligand unbinding. |
format | Online Article Text |
id | pubmed-9402392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-94023922022-08-25 The role of C-terminal helix in the conformational transition of an arginine binding protein Santhakumar, Vinothini Manuel Mascarenhas, Nahren J Struct Biol X Research Article The thermotoga maritima arginine binding protein (TmArgBP) is a periplasmic binding protein that has a short helix at the C-terminal end (CTH), which is swapped between the two chains. We apply a coarse-grained structure-based model (SBM) and all-atom MD simulation on this protein to understand the mechanism and the role of CTH in the conformational transition. When the results of SBM simulations of TmArgBP in the presence and absence of CTH are compared, we find that CTH is strategically located at the back of the binding pocket restraining the open-state conformation thereby disengaging access to the closed-state. We also ran all-atom MD simulations of open-state TmArgBP with and without CTH and discovered that in the absence of CTH the protein could reach the closed-state within 250 ns, while in its presence, the protein remained predominantly in its open-state conformation. In the simulation started from unliganded closed-state conformation without CTH, the protein exhibited multiple transitions between the two states, suggesting CTH as an essential structural element to stabilize the open-state conformation. In another simulation that began with an unliganded closed-state conformation with CTH, the protein was able to access the open-state. In this simulation the CTH was observed to reorient itself to interact with the protein emphasizing its role in assisting the conformational change. Based on our findings, we believe that CTH not only acts as a structural element that constraints the protein in its open-state but it may also guide the protein back to its open-state conformation upon ligand unbinding. Elsevier 2022-08-10 /pmc/articles/PMC9402392/ /pubmed/36035778 http://dx.doi.org/10.1016/j.yjsbx.2022.100071 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Santhakumar, Vinothini Manuel Mascarenhas, Nahren The role of C-terminal helix in the conformational transition of an arginine binding protein |
title | The role of C-terminal helix in the conformational transition of an arginine binding protein |
title_full | The role of C-terminal helix in the conformational transition of an arginine binding protein |
title_fullStr | The role of C-terminal helix in the conformational transition of an arginine binding protein |
title_full_unstemmed | The role of C-terminal helix in the conformational transition of an arginine binding protein |
title_short | The role of C-terminal helix in the conformational transition of an arginine binding protein |
title_sort | role of c-terminal helix in the conformational transition of an arginine binding protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402392/ https://www.ncbi.nlm.nih.gov/pubmed/36035778 http://dx.doi.org/10.1016/j.yjsbx.2022.100071 |
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