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

作者：Atherton Joseph; Jiang Kai; Stangier Marcel M; Luo Yanzhang; Hua Shasha; Houben Klaartje; van Hooff Jolien J E; Joseph Agnel Praveen; Scarabelli Guido; Grant Barry J; Roberts Anthony J; Topf Maya; Steinmetz Michel O; Baldus Marc; Moores Carolyn A^*; Akhmanova Anna^*

来源：Nature Structural & Molecular Biology, 2017, 24(11): 931-+.

DOI：10.1038/nsmb.3483

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.

• 出版日期2017-11