The DCX-domain tandems of doublecortin and doublecortin-like kinase

Myung Hee Kim, Tomasz Cierpicki, Urszula Derewenda, Daniel Krowarsch, Yuanyi Feng, Yancho Devedjiev, Zbigniew Dauter, Christopher A. Walsh, Jacek Otlewski, John H. Bushweller, Zygmunt S. Derewenda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

The doublecortin-like domains (DCX), which typically occur in tandem, are novel microtubule-binding modules. DCX tandems are found in doublecortin, a 360-residue protein expressed in migrating neurons; the doublecortinlike kinase (DCLK); the product of the RP1 gene that is responsible for a form of inherited blindness; and several other proteins. Mutations in the gene encoding doublecortin cause lissencephaly in males and the 'double-cortex syndrome' in females. We here report a solution structure of the N-terminal DCX domain of human doublecortin and a 1.5 Å resolution crystal structure of the equivalent domain from human DCLK. Both show a stable, ubiquitin-like tertiary fold with distinct structural similarities to GTPase-binding domains. We also show that the C-terminal DCX domains of both proteins are only partially folded. In functional assays, the N-terminal DCX domain of doublecortin binds only to assembled microtubules, whereas the C-terminal domain binds to both microtubules and unpolymerized tubulin.

Original languageEnglish (US)
Pages (from-to)324-333
Number of pages10
JournalNature Structural Biology
Volume10
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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