| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Wolny, Marcin Peckham, Michelle Ogawa, Hiromi Earnshaw, William C. Platani, Melpomeni Knight, Peter J. Samejima, Kumiko Vargiu, Giulia |
| Description |
Author Affiliation: Samejima K ( From The Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom and kumiko.samejima@ed.ac.uk.); Platani M ( From The Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom and.); Wolny M ( The Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.); Ogawa H ( From The Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom and.); Vargiu G ( From The Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom and.); Knight PJ ( The Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.); Peckham M ( The Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom M.Peckham@leeds.ac.uk.); Earnshaw WC ( From The Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom and bill.earnshaw@ed.ac.uk.) |
| Abstract |
The chromosome passenger complex (CPC) is a master regulator of mitosis. Inner centromere protein (INCENP) acts as a scaffold regulating CPC localization and activity. During early mitosis, the N-terminal region of INCENP forms a three-helix bundle with Survivin and Borealin, directing the CPC to the inner centromere where it plays essential roles in chromosome alignment and the spindle assembly checkpoint. The C-terminal IN box region of INCENP is responsible for binding and activating Aurora B kinase. The central region of INCENP has been proposed to comprise a coiled coil domain acting as a spacer between the N- and C-terminal domains that is involved in microtubule binding and regulation of the spindle checkpoint. Here we show that the central region (213 residues) of chicken INCENP is not a coiled coil but a ∼32-nm-long single α-helix (SAH) domain. The N-terminal half of this domain directly binds to microtubules in vitro. By analogy with previous studies of myosin 10, our data suggest that the INCENP SAH might stretch up to ∼80 nm under physiological forces. Thus, the INCENP SAH could act as a flexible “dog leash,” allowing Aurora B to phosphorylate dynamic substrates localized in the outer kinetochore while at the same time being stably anchored to the heterochromatin of the inner centromere. Furthermore, by achieving this flexibility via an SAH domain, the CPC avoids a need for dimerization (required for coiled coil formation), which would greatly complicate regulation of the proximity-induced trans-phosphorylation that is critical for Aurora B activation. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
35 |
| Volume Number |
290 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2015-08-28 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Chromosomal Proteins, Non-Histone Chemistry Metabolism Chromosomes Microtubules Mitosis Amino Acid Sequence Animals Aurora Kinase B Cell Line Cell Proliferation Models, Biological Molecular Sequence Data Mutant Proteins Mutation Phosphorylation Protein Binding Protein Stability Protein Structure, Secondary Protein Structure, Tertiary Structure-Activity Relationship Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
