6J4O

Structural basis of tubulin detyrosination by vasohibins-SVBP enzyme complex and functional implications

Summary for 6J4O

• Entry DOI: 10.2210/pdb6j4o/pdb
• Descriptor: Tubulinyl-Tyr carboxypeptidase 2, Small vasohibin-binding protein, GLYCEROL, ... (5 entities in total)
• Functional Keywords: carboxypeptidase, tubulin, microtubule, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 38640.07

Authors

Wang, N.,Huang, H. (deposition date: 2019-01-10, release date: 2019-05-01, Last modification date: 2024-11-13)

Primary citation

Wang, N.,Bosc, C.,Ryul Choi, S.,Boulan, B.,Peris, L.,Olieric, N.,Bao, H.,Krichen, F.,Chen, L.,Andrieux, A.,Olieric, V.,Moutin, M.J.,Steinmetz, M.O.,Huang, H.
Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex.
Nat.Struct.Mol.Biol., 26:571-582, 2019

PubMed Abstract: Vasohibins are tubulin tyrosine carboxypeptidases that are important in neuron physiology. We examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal α-tubulin peptide. In combination with functional data, we propose that SVBP acts as an activator of vasohibins. An extended groove and a distinctive surface residue patch of vasohibins define the specific determinants for recognizing and cleaving the C-terminal tyrosine of α-tubulin and for binding microtubules, respectively. The vasohibin-SVBP interaction and the ability of the enzyme complex to associate with microtubules regulate axon specification of neurons. Our results define the structural basis of tubulin detyrosination by vasohibins and show the relevance of this process for neuronal development. Our findings offer a unique platform for developing drugs against human conditions with abnormal tubulin tyrosination levels, such as cancer, heart defects and possibly brain disorders.

PubMed: 31235911
DOI: 10.1038/s41594-019-0241-y

Experimental method

X-RAY DIFFRACTION (2.3 Å)