研究人员使用单倍体遗传筛选来确定了一个未被命名的蛋白，MATCAP，作为一个剩余的脱酪氨酸化酶。X射线晶体学和冷冻电镜结构确定了MATCAP的切割机制、底物特异性和微管识别。矛盾的是，虽然废除酪氨酸再结合在小鼠中是致命的，但MATCAP和SVBP的共同缺失则不是。
虽然可以存活，但缺陷的脱酪氨酸化导致小头畸形，与神经发生期间的增殖缺陷和异常行为有关。因此，MATCAP是脱酪氨酸化-酪氨酸化循环中的一个缺失成分，并揭示了这种修饰在大脑形成中的重要性。
据介绍，脱酪氨酸化-酪氨酸化循环涉及α-管蛋白C端酪氨酸的去除和重新连接，并与认知、心脏和有丝分裂缺陷有关。Vasohibin-SVBP复合物是大部分（但不是全部）脱酪氨酸化的基础。
附：英文原文
Title: Posttranslational modification of microtubules by the MATCAP detyrosinase
Author: Lisa 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
Issue&Volume: 2022-04-28
Abstract: The detyrosination-tyrosination cycle involves the removal and re-ligation of the C-terminal tyrosine of α-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.
DOI: abn6020
Source: https://www.science.org/doi/10.1126/science.abn6020