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

Nat Struct Biol. 2003 May;10(5):324-33. doi: 10.1038/nsb918.

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 doublecortin-like 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 A 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Brain / abnormalities
  • Calcium-Calmodulin-Dependent Protein Kinases / chemistry*
  • Conserved Sequence
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Doublecortin-Like Kinases
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Microtubule-Associated Proteins*
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / chemistry*
  • Neuropeptides / chemistry*
  • Phosphoproteins / chemistry
  • Protein Conformation
  • Protein Serine-Threonine Kinases*
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Intracellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Phosphoproteins
  • DCLK1 protein, human
  • Doublecortin-Like Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases

Associated data

  • PDB/1MFW
  • PDB/1MG4
  • PDB/1MJD