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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...

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Autores principales: Ikeda, Akihito, Urata, Seia, Ando, Tadashi, Suzuki, Yasuhiro, Sato, Yasufumi, Nishino, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2020
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.
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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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