7Z6S

MATCAP bound to a human 14 protofilament microtubule

Summary for 7Z6S

• Entry DOI: 10.2210/pdb7z6s/pdb
• Related: 7Z5G 7Z5H
• EMDB information: 14529
• Descriptor: Tubulin alpha-1B chain, Tubulin beta-3 chain, Uncharacterized protein KIAA0895-like, ... (7 entities in total)
• Functional Keywords: detyrosination, microtubule-binding, zinc-metalloprotease, tyrosine carboxypeptidase, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 313771.27

Authors

Bak, J.,Perrakis, A. (deposition date: 2022-03-14, release date: 2022-05-11, Last modification date: 2024-10-16)

Primary citation

Landskron, L.,Bak, J.,Adamopoulos, A.,Kaplani, K.,Moraiti, M.,van den Hengel, L.G.,Song, J.Y.,Bleijerveld, O.B.,Nieuwenhuis, J.,Heidebrecht, T.,Henneman, L.,Moutin, M.J.,Barisic, M.,Taraviras, S.,Perrakis, A.,Brummelkamp, T.R.
Posttranslational modification of microtubules by the MATCAP detyrosinase.
Science, 376:eabn6020-eabn6020, 2022

PubMed 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.

PubMed: 35482892
DOI: 10.1126/science.abn6020

Experimental method

ELECTRON MICROSCOPY (2.9 Å)