Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization

Fabrizio Villa, Paola Capasso, Marcello Tortorici, Federico Forneris, Ario De Marco, Andrea Mattevi, Andrea Musacchio

Research output: Contribution to journalArticlepeer-review


Haspin, a nuclear and chromosome-associated serine/threonine (S/T) kinase, is responsible for mitotic phosphorylation of Thr-3 of histone H3. Haspin bears recognizable similarity to the eukaryotic protein kinase (ePK) fold, but its sequence is highly divergent and there is therefore considerable interest in its structural organization. We report the 2.15-Å crystal structure of the kinase domain of human Haspin. The ePK fold of Haspin contains an array of insertions and deletions. The structure illustrates how Haspin escapes the classical activation scheme of most other kinases. The αC helix, which bears a conserved glutamate that is essential for catalysis, adopts its final active conformation within the small lobe of the kinase. It is sandwiched between an α-helical insertion that precedes the kinase domain, and the activation segment, which adopts an unprecedented conformation. The activation segment, which does not contain phosphorylatable residues, packs against an unusually structured αEF helix. Significantly extruded from the core of the fold, it forms an extensive plateau, hosting several residues implicated in substrate binding. Overall, the structure of the Haspin kinase domain reveals an active conformation that is poised for substrate recognition and phosphorylation in the absence of external regulators.

Original languageEnglish
Pages (from-to)20204-20209
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number48
Publication statusPublished - Dec 1 2009


  • Activation segment
  • Centromere
  • Chromosome segregation
  • Histone H3
  • Mitosis

ASJC Scopus subject areas

  • General


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