1mjd: Difference between revisions

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New page: left|200px<br /> <applet load="1mjd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mjd" /> '''Structure of N-terminal domain of human dou...
 
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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, 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.
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MJD OCA].  
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.H.]]
[[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.S.]]
[[Category: Derewenda, Z S.]]
[[Category: Devedjiev, Y.]]
[[Category: Devedjiev, Y.]]
[[Category: Feng, Y.]]
[[Category: Feng, Y.]]
[[Category: Kim, M.H.]]
[[Category: Kim, M H.]]
[[Category: Krowarsch, D.]]
[[Category: Krowarsch, D.]]
[[Category: Otlewski, J.]]
[[Category: Otlewski, J.]]
[[Category: Walsh, C.A.]]
[[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]]


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''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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1mjd

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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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