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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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Detalles Bibliográficos
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
Descripción
Sumario: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.