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TitlePosttranslational modification of microtubules by the MATCAP detyrosinase.
Journal, issue, pagesScience, Vol. 376, Issue 6595, Page eabn6020, Year 2022
Publish dateMay 20, 2022
AuthorsLisa Landskron / Jitske Bak / Athanassios Adamopoulos / Konstantina Kaplani / Maria Moraiti / Lisa G van den Hengel / Ji-Ying Song / Onno B Bleijerveld / Joppe Nieuwenhuis / Tatjana Heidebrecht / Linda Henneman / Marie-Jo Moutin / Marin Barisic / Stavros Taraviras / Anastassis Perrakis / Thijn R Brummelkamp /
PubMed AbstractThe detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of α-tubulin and is implicated in cognitive, cardiac, and mitotic defects. The vasohibin-small ...The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of α-tubulin and is implicated in cognitive, cardiac, and mitotic defects. The vasohibin-small vasohibin-binding protein (SVBP) complex underlies much, but not all, detyrosination. We used haploid genetic screens to identify an unannotated protein, microtubule associated tyrosine carboxypeptidase (MATCAP), as a remaining detyrosinating enzyme. X-ray crystallography and cryo-electron microscopy structures established MATCAP's cleaving mechanism, substrate specificity, and microtubule recognition. Paradoxically, whereas abrogation of tyrosine religation is lethal in mice, codeletion of MATCAP and SVBP is not. Although viable, defective detyrosination caused microcephaly, associated with proliferative defects during neurogenesis, and abnormal behavior. Thus, MATCAP is a missing component of the detyrosination-tyrosination cycle, revealing the importance of this modification in brain formation.
External linksScience / PubMed:35482892
MethodsEM (single particle) / X-ray diffraction
Resolution2.113 - 2.9 Å
Structure data

EMDB-14529, PDB-7z6s:
MATCAP bound to a human 14 protofilament microtubule
Method: EM (single particle) / Resolution: 2.9 Å

PDB-7z5g:
human apo MATCAP
Method: X-RAY DIFFRACTION / Resolution: 2.113 Å

PDB-7z5h:
human Zn MATCAP
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

Chemicals

ChemComp-HOH:
WATER / Water

ChemComp-ZN:
Unknown entry

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

ChemComp-MG:
Unknown entry

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM / Guanosine diphosphate

Source
  • homo sapiens (human)
  • human (human)
KeywordsPEPTIDE BINDING PROTEIN / detyrosination / microtubule-binding / zinc-metalloprotease / tyrosine carboxypeptidase / PROTEIN BINDING

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