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The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core
Vasohibins regulate angiogenesis, tumor growth, metastasis and neuronal differentiation. They form a complex with small vasohibin-binding protein (SVBP) and show tubulin tyrosine carboxypeptidase activity. Recent crystal structure determinations of vasohibin–SVBP complexes have provided a molecular...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543661/ https://www.ncbi.nlm.nih.gov/pubmed/33021501 http://dx.doi.org/10.1107/S2059798320011298 |
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author | Ikeda, Akihito Urata, Seia Ando, Tadashi Suzuki, Yasuhiro Sato, Yasufumi Nishino, Tatsuya |
author_facet | Ikeda, Akihito Urata, Seia Ando, Tadashi Suzuki, Yasuhiro Sato, Yasufumi Nishino, Tatsuya |
author_sort | Ikeda, Akihito |
collection | PubMed |
description | Vasohibins regulate angiogenesis, tumor growth, metastasis and neuronal differentiation. They form a complex with small vasohibin-binding protein (SVBP) and show tubulin tyrosine carboxypeptidase activity. Recent crystal structure determinations of vasohibin–SVBP complexes have provided a molecular basis for complex formation, substrate binding and catalytic activity. However, the regulatory mechanism and dynamics of the complex remain elusive. Here, the crystal structure of the VASH1–SVBP complex and a molecular-dynamics simulation study are reported. The overall structure of the complex was similar to previously reported structures. Importantly, however, the structure revealed a domain-swapped heterotetramer that was formed between twofold symmetry-related molecules. This heterotetramerization was stabilized by the mutual exchange of ten conserved N-terminal residues from the VASH1 structural core, which was intramolecular in other structures. Interestingly, a comparison of this region with previously reported structures revealed that the patterns of hydrogen bonding and hydrophobic interactions vary. In the molecular-dynamics simulations, differences were found between the heterotetramer and heterodimer, where the fluctuation of the N-terminal region in the heterotetramer was suppressed. Thus, heterotetramer formation and flexibility of the N-terminal region may be important for enzyme activity and regulation. |
format | Online Article Text |
id | pubmed-7543661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-75436612020-10-27 The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core Ikeda, Akihito Urata, Seia Ando, Tadashi Suzuki, Yasuhiro Sato, Yasufumi Nishino, Tatsuya Acta Crystallogr D Struct Biol Research Papers Vasohibins regulate angiogenesis, tumor growth, metastasis and neuronal differentiation. They form a complex with small vasohibin-binding protein (SVBP) and show tubulin tyrosine carboxypeptidase activity. Recent crystal structure determinations of vasohibin–SVBP complexes have provided a molecular basis for complex formation, substrate binding and catalytic activity. However, the regulatory mechanism and dynamics of the complex remain elusive. Here, the crystal structure of the VASH1–SVBP complex and a molecular-dynamics simulation study are reported. The overall structure of the complex was similar to previously reported structures. Importantly, however, the structure revealed a domain-swapped heterotetramer that was formed between twofold symmetry-related molecules. This heterotetramerization was stabilized by the mutual exchange of ten conserved N-terminal residues from the VASH1 structural core, which was intramolecular in other structures. Interestingly, a comparison of this region with previously reported structures revealed that the patterns of hydrogen bonding and hydrophobic interactions vary. In the molecular-dynamics simulations, differences were found between the heterotetramer and heterodimer, where the fluctuation of the N-terminal region in the heterotetramer was suppressed. Thus, heterotetramer formation and flexibility of the N-terminal region may be important for enzyme activity and regulation. International Union of Crystallography 2020-09-16 /pmc/articles/PMC7543661/ /pubmed/33021501 http://dx.doi.org/10.1107/S2059798320011298 Text en © Ikeda et al. 2020 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Research Papers Ikeda, Akihito Urata, Seia Ando, Tadashi Suzuki, Yasuhiro Sato, Yasufumi Nishino, Tatsuya The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core |
title | The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core |
title_full | The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core |
title_fullStr | The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core |
title_full_unstemmed | The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core |
title_short | The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core |
title_sort | crystal structure of the tetrameric human vasohibin-1–svbp complex reveals a variable arm region within the structural core |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543661/ https://www.ncbi.nlm.nih.gov/pubmed/33021501 http://dx.doi.org/10.1107/S2059798320011298 |
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