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Cited by 48Microtubule and mitosis dynamicsProtein Structure and DynamicsGenetic and Kidney Cyst Diseases

Structural determinants of microtubule minus end preference in CAMSAP CKK domains

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Atherton, Joseph, Luo, Yanzhang, Xiang, Shengqi, Yang, Chao, Rai, Ankit, Jiang, Kai, Stangier, Marcel, Vemu, Annapurna +7 more·2019·Nature Communications
DOI 10.1038/s41467-019-13247-6PMC PMC6868217

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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.

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  • The inter-protofilament binding mode of the GEFH1 C1 domain resembles that of the CAMSAP1 CKK domain, which also spans two neighboring αβ-tubulin heterodimers, suggesting competition for the same binding site.

    “the inter-protofilament binding mode of the GEFH1 C1 domain resembles that of the CKK domain of calmodulin-regulated spectrin-associated protein 1 (CAMSAP1), which also spans two neighboring αβ-tubulin heterodimers”

    From Structural basis of microtubule-mediated signal transduction (2026) · cites this paper as [37]

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Authors
Atherton, J., Luo, Y., Xiang, S., Yang, C., Rai, A., Jiang, K., Stangier, M., Vemu, A., Cook, A. D., Wang, S., Roll-Mecak, A., Steinmetz, M. O., Akhmanova, A., Baldus, M., & Moores, C. A.
Affiliations
  • Institute of Structural and Molecular Biology (GB)
  • Utrecht University (NL)
  • University of Science and Technology of China (CN)
  • Wuhan University (CN)
  • Paul Scherrer Institute (CH)
  • National Institute of Neurological Disorders and Stroke (US)
  • University of Basel (CH)
Corresponding author
  • Atherton, Joseph
  • Baldus, Marc
  • Moores, Carolyn A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-11-20
Volume
10
Issue
1
Pages
5236-5236
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-13247-6
PMC
PMC6868217
OpenAlex
W2991157552
Cited by
48
References
0
Citations by year
2026: 6 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 4 · 2019: 2
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BIROn (Birkbeck, University of London) (acceptedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Wellcome Trust (079605, 079605/Z/06/Z)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (166608)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (718.015.001, 175.010.200, 722.016.002, 184.032.207, 175.010.2009.002)
  • China Scholarship Council
  • Directorate for Biological Sciences
  • Medical Research Council (MR/R000352/1)
  • Biotechnology and Biological Sciences Research Council (BB/L014211/1)
  • National Heart, Lung, and Blood Institute
  • National Institute of Neurological Disorders and Stroke
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
microtubule minus ends, microtubule dynamics, tubulin conformation, Naegleria gruberi, microtubule-binding protein, microtubule lattice, protein rigidity
MeSH terms
Protein Domains, Humans, Microtubule-Associated Proteins, Microtubules, Models, Molecular, Naegleria, Magnetic Resonance Spectroscopy, Protein Binding, Tubulin, Cryoelectron Microscopy

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