The inner centromere protein (INCENP) coil is a single α-helix (SAH) domain that binds directly to microtubules and is important for chromosome passenger complex (CPC) localization and function in mitosis

Kumiko Samejima, Melpomeni Platani, Marcin Wolny, Hiromi Ogawa, Giulia Vargiu, Peter J. Knight, Michelle Peckham, William C. Earnshaw

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)21460-21472
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number35
DOIs
Publication statusPublished - 28 Aug 2015

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