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

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CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize non-centrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we show that the C-terminal CKK domain of CAMSAPs is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncover how mammalian CKK binds between two tubulin dimers at the inter-protofilament interface on the outer microtubule surface. In vitro reconstitution assays combined with high resolution fluorescence microscopy and cryo-electron tomography suggest 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 inter-protofilament interface at this site form 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.