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The crystal structure of the tetrameric human vasohibin-1–SVBP complex reveals a variable arm region within the structural core
- Source :
- Acta Crystallographica. Section D, Structural Biology
- Publication Year :
- 2020
- Publisher :
- International Union of Crystallography (IUCr), 2020.
-
Abstract
- Vasohibin-1 and small vasohibin-binding protein (SVBP) form an intermolecular heterotetramer in the crystal. The heterotetramer was stabilized by exchange of the conserved N-terminal region.<br />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.
- Subjects :
- Models, Molecular
vasohibin
Cell Cycle Proteins
Crystal structure
Crystallography, X-Ray
Hydrophobic effect
Carboxypeptidase activity
03 medical and health sciences
0302 clinical medicine
Protein Domains
Structural Biology
Humans
Molecule
030304 developmental biology
MD simulations
0303 health sciences
Chemistry
Hydrogen bond
protein complex
microtubule modification
Substrate (chemistry)
VASH1–SVBP complex
small vasohibin-binding protein
X-ray crystal structure
Research Papers
Heterotetramer
Intramolecular force
Biophysics
Protein Multimerization
Carrier Proteins
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20597983
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- Acta Crystallographica Section D Structural Biology
- Accession number :
- edsair.doi.dedup.....f970aaa7a38ed0b1fe15c932b06658ca