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Mol Biol Cell. 2018 Feb 1;29(3):285-294. doi: 10.1091/mbc.E17-01-0057. Epub 2017 Nov 29.

Stu2 uses a 15-nm parallel coiled coil for kinetochore localization and concomitant regulation of the mitotic spindle.

Author information

1
Molecular and Cellular Biophysics Program, University of North Carolina, Chapel Hill, NC 27599.
2
Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
3
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599.
4
Department of Biology, University of North Carolina, Chapel Hill, NC 27599.
5
Department of Biology, University of North Carolina, Chapel Hill, NC 27599 kslep@bio.unc.edu.

Abstract

XMAP215/Dis1 family proteins are potent microtubule polymerases, critical for mitotic spindle structure and dynamics. While microtubule polymerase activity is driven by an N-terminal tumor overexpressed gene (TOG) domain array, proper cellular localization is a requisite for full activity and is mediated by a C-terminal domain. Structural insight into the C-terminal domain's architecture and localization mechanism remain outstanding. We present the crystal structure of the Saccharomyces cerevisiae Stu2 C-terminal domain, revealing a 15-nm parallel homodimeric coiled coil. The parallel architecture of the coiled coil has mechanistic implications for the arrangement of the homodimer's N-terminal TOG domains during microtubule polymerization. The coiled coil has two spatially distinct conserved regions: CRI and CRII. Mutations in CRI and CRII perturb the distribution and localization of Stu2 along the mitotic spindle and yield defects in spindle morphology including increased frequencies of mispositioned and fragmented spindles. Collectively, these data highlight roles for the Stu2 dimerization domain as a scaffold for factor binding that optimally positions Stu2 on the mitotic spindle to promote proper spindle structure and dynamics.

PMID:
29187574
PMCID:
PMC5996958
DOI:
10.1091/mbc.E17-01-0057
[Indexed for MEDLINE]
Free PMC Article

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