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TitleCryo-EM structure of VASH1-SVBP bound to microtubules.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateAug 10, 2020
AuthorsFaxiang Li / Yang Li / Xuecheng Ye / Haishan Gao / Zhubing Shi / Xuelian Luo / Luke M Rice / Hongtao Yu /
PubMed AbstractThe dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The ...The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate α-tubulin detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble αβ-tubulin heterodimers. The structural basis for this substrate preference is not understood. Using cryo-electron microscopy (cryo-EM), we have determined the structure of human VASH1-SVBP bound to microtubules. The acidic C-terminal tail of α-tubulin binds to a positively charged groove near the active site of VASH1. VASH1 forms multiple additional contacts with the globular domain of α-tubulin, including contacts with a second α-tubulin in an adjacent protofilament. Simultaneous engagement of two protofilaments by VASH1 can only occur within the microtubule lattice, but not with free αβ heterodimers. These lattice-specific interactions enable preferential detyrosination of microtubules by VASH1.
External linksElife / PubMed:32773040 / PubMed Central
MethodsEM (single particle)
Resolution3.1 Å
Structure data

EMDB-21893, PDB-6wsl:
Cryo-EM structure of VASH1-SVBP bound to microtubules
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-G2P:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-CPP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsPROTEIN BINDING / Microtubule / Posttranslational modification / Detyrosination / Vasohibin

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