6LPG

human VASH1-SVBP complex

Summary for 6LPG

• Entry DOI: 10.2210/pdb6lpg/pdb
• Descriptor: Tubulinyl-Tyr carboxypeptidase 1, Small vasohibin-binding protein, SULFATE ION, ... (4 entities in total)
• Functional Keywords: tubulin carboxypeptidases, microtubule modification, angiogenesis, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 37526.07

Authors

Ikeda, A.,Nishino, T. (deposition date: 2020-01-10, release date: 2020-10-21, Last modification date: 2023-11-29)

Primary citation

Ikeda, A.,Urata, S.,Ando, T.,Suzuki, Y.,Sato, Y.,Nishino, T.
The crystal structure of the tetrameric human vasohibin-1-SVBP complex reveals a variable arm region within the structural core.
Acta Crystallogr D Struct Biol, 76:993-1000, 2020

PubMed Abstract: 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.

PubMed: 33021501
DOI: 10.1107/S2059798320011298

Experimental method

X-RAY DIFFRACTION (2.3 Å)