Format

Send to

Choose Destination
Nat Struct Mol Biol. 2017 Nov;24(11):931-943. doi: 10.1038/nsmb.3483. Epub 2017 Oct 9.

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

Author information

1
Institute of Structural and Molecular Biology, Birkbeck, University of London, London, UK.
2
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
3
Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland.
4
NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands.
5
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, the Netherlands.
6
Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
7
Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
8
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
9
Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
10
University of Basel, Biozentrum, Basel, Switzerland.

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.

PMID:
28991265
PMCID:
PMC6134180
DOI:
10.1038/nsmb.3483
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center