1mjd: Difference between revisions
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'''Structure of N-terminal domain of human doublecortin'''<br /> | '''Structure of N-terminal domain of human doublecortin'''<br /> | ||
==Overview== | ==Overview== | ||
The doublecortin-like domains (DCX), which typically occur in tandem, are | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1MJD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1MJD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MJD OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bushweller, J | [[Category: Bushweller, J H.]] | ||
[[Category: Cierpicki, T.]] | [[Category: Cierpicki, T.]] | ||
[[Category: Dauter, Z.]] | [[Category: Dauter, Z.]] | ||
[[Category: Derewenda, U.]] | [[Category: Derewenda, U.]] | ||
[[Category: Derewenda, Z | [[Category: Derewenda, Z S.]] | ||
[[Category: Devedjiev, Y.]] | [[Category: Devedjiev, Y.]] | ||
[[Category: Feng, Y.]] | [[Category: Feng, Y.]] | ||
[[Category: Kim, M | [[Category: Kim, M H.]] | ||
[[Category: Krowarsch, D.]] | [[Category: Krowarsch, D.]] | ||
[[Category: Otlewski, J.]] | [[Category: Otlewski, J.]] | ||
[[Category: Walsh, C | [[Category: Walsh, C A.]] | ||
[[Category: dcx domain]] | [[Category: dcx domain]] | ||
[[Category: microtubule associated protein]] | [[Category: microtubule associated protein]] | ||
[[Category: ubiquitin-like fold]] | [[Category: ubiquitin-like fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:55:42 2008'' |
Revision as of 14:55, 21 February 2008
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Structure of N-terminal domain of human doublecortin
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Lissencephaly, X-linked OMIM:[300121], Subcortical laminal heteropia, X-linked OMIM:[300121]
About this StructureAbout this Structure
1MJD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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