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Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain
Guanosine 5′-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-β-synthase (CBS) domain, though the role of this domain is not full...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160140/ https://www.ncbi.nlm.nih.gov/pubmed/32296055 http://dx.doi.org/10.1038/s41467-020-15611-3 |
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author | Imamura, Akira Okada, Tetsuya Mase, Hikaru Otani, Takuya Kobayashi, Tomoka Tamura, Manatsu Kubata, Bruno Kilunga Inoue, Katsuaki Rambo, Robert P. Uchiyama, Susumu Ishii, Kentaro Nishimura, Shigenori Inui, Takashi |
author_facet | Imamura, Akira Okada, Tetsuya Mase, Hikaru Otani, Takuya Kobayashi, Tomoka Tamura, Manatsu Kubata, Bruno Kilunga Inoue, Katsuaki Rambo, Robert P. Uchiyama, Susumu Ishii, Kentaro Nishimura, Shigenori Inui, Takashi |
author_sort | Imamura, Akira |
collection | PubMed |
description | Guanosine 5′-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-β-synthase (CBS) domain, though the role of this domain is not fully understood. Here, we show that guanine and adenine nucleotides exert positive and negative effects, respectively, on TbGMPR activity by binding allosterically to the CBS domain. The present structural analyses revealed that TbGMPR forms an octamer that shows a transition between relaxed and twisted conformations in the absence and presence of guanine nucleotides, respectively, whereas the TbGMPR octamer dissociates into two tetramers when ATP is available instead of guanine nucleotides. These findings demonstrate that the CBS domain plays a key role in the allosteric regulation of TbGMPR by facilitating the transition of its oligomeric state depending on ligand nucleotide availability. |
format | Online Article Text |
id | pubmed-7160140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71601402020-04-22 Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain Imamura, Akira Okada, Tetsuya Mase, Hikaru Otani, Takuya Kobayashi, Tomoka Tamura, Manatsu Kubata, Bruno Kilunga Inoue, Katsuaki Rambo, Robert P. Uchiyama, Susumu Ishii, Kentaro Nishimura, Shigenori Inui, Takashi Nat Commun Article Guanosine 5′-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-β-synthase (CBS) domain, though the role of this domain is not fully understood. Here, we show that guanine and adenine nucleotides exert positive and negative effects, respectively, on TbGMPR activity by binding allosterically to the CBS domain. The present structural analyses revealed that TbGMPR forms an octamer that shows a transition between relaxed and twisted conformations in the absence and presence of guanine nucleotides, respectively, whereas the TbGMPR octamer dissociates into two tetramers when ATP is available instead of guanine nucleotides. These findings demonstrate that the CBS domain plays a key role in the allosteric regulation of TbGMPR by facilitating the transition of its oligomeric state depending on ligand nucleotide availability. Nature Publishing Group UK 2020-04-15 /pmc/articles/PMC7160140/ /pubmed/32296055 http://dx.doi.org/10.1038/s41467-020-15611-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Imamura, Akira Okada, Tetsuya Mase, Hikaru Otani, Takuya Kobayashi, Tomoka Tamura, Manatsu Kubata, Bruno Kilunga Inoue, Katsuaki Rambo, Robert P. Uchiyama, Susumu Ishii, Kentaro Nishimura, Shigenori Inui, Takashi Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain |
title | Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain |
title_full | Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain |
title_fullStr | Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain |
title_full_unstemmed | Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain |
title_short | Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-β-synthase domain |
title_sort | allosteric regulation accompanied by oligomeric state changes of trypanosoma brucei gmp reductase through cystathionine-β-synthase domain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160140/ https://www.ncbi.nlm.nih.gov/pubmed/32296055 http://dx.doi.org/10.1038/s41467-020-15611-3 |
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