Structural determinants of microtubule minus end preference in CAMSAP CKK domains
Joseph Atherton, Yanzhang Luo, Shengqi Xiang, Chao Yang , Kai Jiang, Marcel Stangier, Annapurna Vemu, Alexander D. Cook, Su Wang, Antonina Roll-Mecak, Michel O. Steinmetz, Anna Akhmanova, Marc Baldus, and Carolyn A. Moores
Received Date: 13th March 19
CAMSAP/Patronins regulate microtubule minus-end dynamics. Their end specificity is mediated by their CKK domains, which we proposed recognise specific tubulin conformations found at minus ends. To critically test this idea, we compared the human CAMSAP1 CKK domain (HsCKK) with a CKK domain from Naegleria gruberi (NgCKK), which has lost minus-end specificity. Near-atomic cryo-electron microscopy structures of HsCKK- and NgCKK-microtubule complexes show that these CKK domains share the same protein fold, bind at the intradimer interprotofilament tubulin junction, but exhibit subtly different footprints on microtubules. Whereas NgCKK binding does not alter the microtubule architecture, HsCKK remodels its microtubule interaction site and changes the underlying polymer structure because the tubulin lattice conformation is not optimal for its binding. NMR experiments show that HsCKK is remarkably rigid, supporting this remodelling ability. Thus, in contrast to many MAPs, CKK domains can differentiate subtly specific tubulin conformations to enable microtubule minus-end recognition.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.