Year: 2019
Type: article
Abstract: 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 lacks minus-end specificity. Here we report near-atomic cryo-electron microscopy structures of HsCKK- and NgCKK-microtubule complexes, which show that these CKK domains share the same protein fold, bind at the intradimer interprotofilament tubulin junction, but exhibit different footprints on microtubules. NMR experiments show that both HsCKK and NgCKK are remarkably rigid. However, 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. Thus, in contrast to many MAPs, the HsCKK domain can differentiate subtly specific tubulin conformations to enable microtubule minus-end recognition.
Source: Nature Communications
Institutions: Institute of Structural and Molecular Biology, Birkbeck, University of London, Utrecht University, University of Science and Technology of China, Wuhan University, Paul Scherrer Institute, National Institute of Neurological Disorders and Stroke, National Heart, Lung, and Blood Institute, University of Basel
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Science Foundation, Wellcome Trust, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, China Scholarship Council, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke
Awards: Energy filter with direct electron detector for electron cryo tomography, Cryo-electron microscopy equipment for structure determination of macromolecular and cellular assemblies., Caught in the act: a combined magnetic resonance -modelling approach to capture cellular machines at work, G494123624, Building blocks of molecular complexity: the neuronal cytoskeleton in health and disease, G6927657787, Control of Tubulin Structure and Function by Accessory Proteins and Drugs, Cryo-electron microscopy equipment for structure determination of macromolecular and cellular assemblies., An ultra-high field NMR facility for the Netherlands (uNMR-NL), G9000129426
OpenAlex ID: W2991157552