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-Structure paper
タイトル | Posttranslational modification of microtubules by the MATCAP detyrosinase. |
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ジャーナル・号・ページ | Science, Vol. 376, Issue 6595, Page eabn6020, Year 2022 |
掲載日 | 2022年5月20日 |
著者 | 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 / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:35482892 |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.113 - 2.9 Å |
構造データ | EMDB-14529, PDB-7z6s: PDB-7z5g: PDB-7z5h: |
化合物 | ChemComp-HOH: ChemComp-ZN: ChemComp-GTP: ChemComp-MG: ChemComp-GDP: |
由来 |
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キーワード | PEPTIDE BINDING PROTEIN / detyrosination / microtubule-binding / zinc-metalloprotease / tyrosine carboxypeptidase / PROTEIN BINDING (タンパク質) |