Structural basis of tubulin detyrosination by vasohibins

Li, Faxiang; Yingjie, Hu,; Qi, Shu-Tao; Luo, Xuelian; Yu, Hongtao

doi:10.1038/s41594-019-0242-x

Cited by 60 publications

(85 citation statements)

References 37 publications

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“…Such autoinhibition/processing has been observed for the renin prosegment, which binds and forms a -sheet with the protease domain to block the active site (Morales et al, 2012). Interestingly, in the VASH1-SVBP-epoY structure Phe60 of the N-terminal region was close to the epoY inhibitor (Liao et al, 2019), but in other structures, the same Phe60 side-chain rotamer is oriented differently (Li et al, 2019). In the VASH2-SVBP-epoY crystal structure, the corresponding Phe49 was also close to epoY (Wang et al, 2019).…”

Section: Structurementioning

confidence: 68%

“…In the structure, four sulfate ions were bound to the basic surface of VASH1-SVBP. Some of the reported VASH-SVBP structures contained sulfate or phosphate ions bound to the basic surface (Li et al, 2019;. Interestingly, one of the sulfate ions was found in a position close to the catalytic triad and interacted with Tyr134, Ser221 and Arg222 (Fig.…”

Section: Crystal Structure Of the Vash1c-svbp Complexmentioning

confidence: 98%

“…1c). These three amino-acid residues were important in directly recognizing the tubulin peptides and the epoY inhibitor (Liao et al, 2019;Li et al, 2019). Vasohibins are known to bind to the C-terminal tail region of -tubulin, which is rich in glutamate residues.…”

Section: Crystal Structure Of the Vash1c-svbp Complexmentioning

confidence: 99%

“…Sequence analysis of vasohibins identified that they belong to the transglutaminase-like cysteine proteases, with conserved catalytic residues and a putative Ca 2+ -binding site (Sanchez-Pulido & Ponting, 2016). Crystal structures of the vasohibin-SVBP complex revealed that the catalytic site is indeed similar to that of transglutaminase (Adamopoulos et al, 2019;Li et al, 2019;Liao et al, 2019;Wang et al, 2019;Zhou et al, 2019;Liu et al, 2019). SVBP binds to the N-terminal structural core region of vasohibin and stabilizes the complex.…”

Section: Introductionmentioning

confidence: 99%

“…SVBP binds to the N-terminal structural core region of vasohibin and stabilizes the complex. The structures of complexes with tubulin peptides or inhibitors revealed how vasohibin recognizes substrates (Li et al, 2019;Liao et al, 2019;Wang et al, 2019;Zhou et al, 2019). However, little is known about the dynamics and regulation of the vasohibin complex.…”

Section: Introductionmentioning

confidence: 99%

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

Ikeda¹,

Urata²,

Ando³

et al. 2020

Acta Cryst Sect D Struct Biol

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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.

show abstract

Section: Structurementioning

confidence: 68%

Section: Crystal Structure Of the Vash1c-svbp Complexmentioning

confidence: 98%

Section: Crystal Structure Of the Vash1c-svbp Complexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Ikeda¹,

Urata²,

Ando³

et al. 2020

Acta Cryst Sect D Struct Biol

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Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

Fourel

Boscheron

2020

FEBS Letters

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Malformations of cortical development (MCDs) are a group of severe brain malformations associated with intellectual disability and refractory childhood epilepsy. Human missense heterozygous mutations in the 9 α‐tubulin and 10 β‐tubulin isoforms forming the heterodimers that assemble into microtubules (MTs) were found to cause MCDs. However, how a single mutated residue in a given tubulin isoform can perturb the entire microtubule population in a neuronal cell remains a crucial question. Here, we examined 85 MCD‐associated tubulin mutations occurring in TUBA1A, TUBB2, and TUBB3 and their location in a three‐dimensional (3D) microtubule cylinder. Mutations hitting residues exposed on the outer microtubule surface are likely to alter microtubule association with partners, while alteration of intradimer contacts may impair dimer stability and straightness. Other types of mutations are predicted to alter interdimer and lateral contacts, which are responsible for microtubule cohesion, rigidity, and dynamics. MCD‐associated tubulin mutations surprisingly fall into all categories, thus providing unexpected insights into how a single mutation may impair microtubule function and elicit dominant effects in neurons.

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Decoding microtubule detyrosination: enzyme families, structures, and functional implications

Bak,

Brummelkamp,

Perrakis

2024

FEBS Letters

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Microtubules are a major component of the cytoskeleton and can accumulate a plethora of modifications. The microtubule detyrosination cycle is one of these modifications; it involves the enzymatic removal of the C‐terminal tyrosine of α‐tubulin on assembled microtubules and the re‐ligation of tyrosine on detyrosinated tubulin dimers. This modification cycle has been implicated in cardiac disease, neuronal development, and mitotic defects. The vasohibin and microtubule‐associated tyrosine carboxypeptidase enzyme families are responsible for microtubule detyrosination. Their long‐sought discovery allows to review and summarise differences and similarities between the two enzymes families and discuss how they interplay with other modifications and functions of the tubulin code.

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Structural basis of tubulin detyrosination by vasohibins

Cited by 60 publications

References 37 publications

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

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

Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

Decoding microtubule detyrosination: enzyme families, structures, and functional implications

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