The crystal structure of the tetrameric human vasohibin-1-SVBP complex reveals a variable arm region within the structural core

Akihito Ikeda, Seia Urata, Tadashi Ando, Yasuhiro Suzuki, Yasufumi Sato, Tatsuya Nishino

研究成果: Article査読

抄録

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.

本文言語English
ページ(範囲)993-1000
ページ数8
ジャーナルActa Crystallographica Section D: Structural Biology
76
DOI
出版ステータスPublished - 2020 10 1

ASJC Scopus subject areas

  • 構造生物学

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