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Cryo-EM structure of VASH1-SVBP bound to microtubules

Faxiang Li1, Yang Li2, Xuecheng Ye2,3

  • 1Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.

Elife
|August 11, 2020
PubMed

Insights

The vasohibin-1 (VASH1) enzyme, with its binding partner SVBP, detyrosinates alpha-tubulin on microtubules. Structural analysis reveals VASH1 binds microtubules specifically, explaining its preference over free tubulin.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Cell Biology

Background:

  • The tyrosination-detyrosination cycle of alpha-tubulin is crucial for microtubule function, impacting cell division, neural activity, and heart contraction.
  • Vasohibin-1 (VASH1) and VASH2, complexed with SVBP, are key enzymes responsible for alpha-tubulin detyrosination.
  • VASH enzymes exhibit higher efficiency in detyrosinating microtubules compared to soluble alpha-beta tubulin heterodimers, a phenomenon lacking structural explanation.

Purpose of the Study:

  • To elucidate the structural basis for the substrate preference of VASH1-SVBP towards microtubules over soluble tubulin.
  • To understand the molecular interactions governing the preferential detyrosination of microtubules by VASH1.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was employed to determine the structure of human VASH1-SVBP bound to microtubules.
  • Detailed structural analysis of the VASH1-SVBP-microtubule complex.

Main Results:

  • The structure reveals that the acidic C-terminal tail of alpha-tubulin interacts with a positively charged groove on VASH1.
  • VASH1 establishes additional contacts with the globular domain of alpha-tubulin, including interactions with a second alpha-tubulin subunit in an adjacent protofilament.
  • VASH1's ability to simultaneously engage two protofilaments is exclusive to the microtubule lattice structure, not possible with free tubulin heterodimers.

Conclusions:

  • VASH1-SVBP preferentially detyrosinates microtubules due to specific lattice interactions that cannot occur with soluble tubulin.
  • These lattice-specific interactions explain the observed substrate preference and the functional importance of the VASH1-SVBP-microtubule complex in regulating microtubule dynamics.
Keywords:
E. colicryo-electron microscopydetyrosinationmicrotubulemolecular biophysicsposttranslational modificationstructural biologyvasohibin

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