A structural model for microtubule minus-end recognition and protection by CAMSAP proteins

Abstract

CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncovered how mammalian CKK binds between two tubulin dimers at the interprotofilament interface on the outer microtubule surface. In vitro reconstitution assays combined with high-resolution fluorescence microscopy and cryo-electron tomography suggested that CKK preferentially associates with the transition zone between curved protofilaments and the regular microtubule lattice. We propose that minus-end-specific features of the interprotofilament interface at this site serve as the basis for CKK's minus-end preference. The steric clash between microtubule-bound CKK and kinesin motors explains how CKK protects microtubule minus ends against kinesin-13-induced depolymerization and thus controls the stability of free microtubule minus ends.

DOI: 10.1038/nsmb.3483

Cite this paper

@article{Atherton2017ASM, title={A structural model for microtubule minus-end recognition and protection by CAMSAP proteins}, author={Joseph Atherton and Kai Jiang and Marcel M Stangier and Yanzhang Luo and Shasha Hua and Klaartje Houben and Jolien Je van Hooff and A Joseph and Guido Scarabelli and Barry J. Grant and Anthony J. Roberts and Maya Topf and Michel O. Steinmetz and Marc Baldus and Carolyn A Moores and Anna Akhmanova}, journal={Nature Structural & Molecular Biology}, year={2017}, volume={24}, pages={931-943} }