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The crystal structure of the tetrameric human vasohibin‐1–SVBP complex reveals a variable arm region within the structural core
Author(s) -
Ikeda Akihito,
Urata Seia,
Ando Tadashi,
Suzuki Yasuhiro,
Sato Yasufumi,
Nishino Tatsuya
Publication year - 2020
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798320011298
Subject(s) - heterotetramer , chemistry , molecular dynamics , stereochemistry , crystal structure , protein structure , crystallography , salt bridge , biophysics , biochemistry , computational chemistry , biology , mutant , protein subunit , gene
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.