Posttranslational modification of microtubules by the MATCAP detyrosinase.
Science
; 376(6595): eabn6020, 2022 05 20.
Article
en En
| MEDLINE
| ID: mdl-35482892
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tirosina
/
Tubulina (Proteína)
/
Carboxipeptidasas
/
Procesamiento Proteico-Postraduccional
/
Proteínas Asociadas a Microtúbulos
/
Microtúbulos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Países Bajos