Structural and Functional Organization of the Ska Complex, a Key Component of the Kinetochore-Microtubule Interface

Jeyaprakash Arulanandam, Anna Santamaria, Uma Jayachandran, Ying Wai Chan, Christian Benda, Erich A. Nigg, Elena Conti

Research output: Contribution to journalArticlepeer-review

Abstract

The Ska complex is an essential mitotic component required for accurate cell division in human cells. It is composed of three subunits that function together to establish stable kinetochore-microtubule interactions in concert with the Ndc80 network. We show that the structure of the Ska core complex is a W-shaped dimer of coiled coils, formed by intertwined interactions between Ska1, Ska2, and Ska3. The C-terminal domains of Skal and Ska3 protrude at each end of the homodimer, bind microtubules in vitro when connected to the central core, and are essential in vivo. Mutations disrupting the central coiled coil or the dimerization interface result in chromosome congression failure followed by cell death. The Ska complex is thus endowed with bipartite and cooperative tubulin-binding properties at the ends of a 350 angstrom-long molecule. We discuss how this symmetric architecture might complement and stabilize the Ndc80-microtubule attachments with analogies to the yeast Dam1/DASH complex.

Original languageEnglish
Pages (from-to)274-286
Number of pages13
JournalMolecular Cell
Volume46
Issue number3
DOIs
Publication statusPublished - 11 May 2012

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