7z5h
human Zn MATCAP
Structural highlights
FunctionMACA1_HUMAN Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:35482892). Also able to remove the C-terminal phenylalanine residue of alpha-tubulin TUBA8 (PubMed:35482892). Recognizes adjacent tubulin dimers along the same protofilament (PubMed:35482892).[1] Publication Abstract from PubMedThe 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. References
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