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Publication Abstract from PubMed

The detyrosination-tyrosination cycle involves the removal and re-ligation of the C-terminal tyrosine of alpha-tubulin and is implicated in cognitive, cardiac, and mitotic defects. The Vasohibin-SVBP complex underlies much, but not all, detyrosination. Here, we used haploid genetic screens to identify an unannotated protein, MATCAP, as a remaining detyrosinating enzyme. X-ray crystallography and cryo-EM structures established MATCAP's cleaving mechanism, substrate specificity, and microtubule recognition. Paradoxically, while abrogation of tyrosine re-ligation is lethal in mice, co-deletion of MATCAP and SVBP was 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.

Posttranslational modification of microtubules by the MATCAP detyrosinase.,Landskron L, Bak J, Adamopoulos A, Kaplani K, Moraiti M, van den Hengel LG, Song JY, Bleijerveld OB, Nieuwenhuis J, Heidebrecht T, Henneman L, Moutin MJ, Barisic M, Taraviras S, Perrakis A, Brummelkamp TR Science. 2022 Apr 28:eabn6020. doi: 10.1126/science.abn6020. PMID:35482892^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.