The DCX-domain tandems of doublecortin and doublecortin-like kinase.
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.
Kim
Myung Hee
MH
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908-0736, USA.
Cierpicki
Tomasz
T
Derewenda
Urszula
U
Krowarsch
Daniel
D
Feng
Yuanyi
Y
Devedjiev
Yancho
Y
Dauter
Zbigniew
Z
Walsh
Christopher A
CA
Otlewski
Jacek
J
Bushweller
John H
JH
Derewenda
Zygmunt S
ZS
D000595:Amino Acid Sequence; D001665:Binding Sites; D001921:Brain / Q000002:abnormalities; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry*; D017124:Conserved Sequence; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009479:Neuropeptides / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases