1mjd

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1mjd

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Structure of N-terminal domain of human doublecortin

Contents

Overview

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.

Disease

Known diseases associated with this structure: Lissencephaly, X-linked OMIM:[300121], Subcortical laminal heteropia, X-linked OMIM:[300121]

About this Structure

1MJD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The DCX-domain tandems of doublecortin and doublecortin-like kinase., Kim MH, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh CA, Otlewski J, Bushweller JH, Derewenda ZS, Nat Struct Biol. 2003 May;10(5):324-33. PMID:12692530

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