2bqq
From Proteopedia
(New page: 200px<br /> <applet load="2bqq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bqq, resolution 2.200Å" /> '''X-RAY STRUCURE OF ...) |
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| - | [[Image:2bqq.gif|left|200px]]<br /> | + | [[Image:2bqq.gif|left|200px]]<br /><applet load="2bqq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2bqq" size=" | + | |
caption="2bqq, resolution 2.200Å" /> | caption="2bqq, resolution 2.200Å" /> | ||
'''X-RAY STRUCURE OF THE N-TERMINAL DOMAIN OF HUMAN DOUBLECORTIN'''<br /> | '''X-RAY STRUCURE OF THE N-TERMINAL DOMAIN OF HUMAN DOUBLECORTIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The doublecortin-like (DC) domains, which usually occur in tandem, constitute novel microtubule-binding modules. They were first identified | + | The doublecortin-like (DC) domains, which usually occur in tandem, constitute novel microtubule-binding modules. They were first identified in doublecortin (DCX), a protein expressed in migrating neurons, and in the doublecortin-like kinase (DCLK). They are also found in other proteins, including the RP1 gene product which-when mutated-causes a form of inherited blindness. We previously reported an X-ray structure of the N-terminal DC domain of DCLK (N-DCLK), and a solution structure of an analogous module of human doublecortin (N-DCX). These studies showed that the DC domain has a tertiary fold closely reminiscent of ubiquitin and similar to several GTPase-binding domains. We now report an X-ray structure of a mutant of N-DCX, in which the C-terminal fragment (residues 139-147) unexpectedly shows an altered, "open" conformation. However, heteronuclear NMR data show that this C-terminal fragment is only transiently open in solution, and assumes a predominantly "closed" conformation. While the "open" conformation may be artificially stabilized by crystal packing interactions, the observed switching between the "open" and "closed" conformations, which shortens the linker between the two DC-domains by approximately 20 A, is likely to be of functional importance in the control of tubulin polymerization and microtubule bundling by doublecortin. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BQQ 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:// | + | 2BQQ 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=2BQQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cooper, D | + | [[Category: Cooper, D R.]] |
[[Category: Derewenda, U.]] | [[Category: Derewenda, U.]] | ||
| - | [[Category: Derewenda, Z | + | [[Category: Derewenda, Z S.]] |
| - | [[Category: Kim, M | + | [[Category: Kim, M H.]] |
[[Category: dcx domain]] | [[Category: dcx domain]] | ||
[[Category: microtubule associated]] | [[Category: microtubule associated]] | ||
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[[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 16:40:40 2008'' |
Revision as of 14:40, 21 February 2008
|
X-RAY STRUCURE OF THE N-TERMINAL DOMAIN OF HUMAN DOUBLECORTIN
Contents |
Overview
The doublecortin-like (DC) domains, which usually occur in tandem, constitute novel microtubule-binding modules. They were first identified in doublecortin (DCX), a protein expressed in migrating neurons, and in the doublecortin-like kinase (DCLK). They are also found in other proteins, including the RP1 gene product which-when mutated-causes a form of inherited blindness. We previously reported an X-ray structure of the N-terminal DC domain of DCLK (N-DCLK), and a solution structure of an analogous module of human doublecortin (N-DCX). These studies showed that the DC domain has a tertiary fold closely reminiscent of ubiquitin and similar to several GTPase-binding domains. We now report an X-ray structure of a mutant of N-DCX, in which the C-terminal fragment (residues 139-147) unexpectedly shows an altered, "open" conformation. However, heteronuclear NMR data show that this C-terminal fragment is only transiently open in solution, and assumes a predominantly "closed" conformation. While the "open" conformation may be artificially stabilized by crystal packing interactions, the observed switching between the "open" and "closed" conformations, which shortens the linker between the two DC-domains by approximately 20 A, is likely to be of functional importance in the control of tubulin polymerization and microtubule bundling by doublecortin.
Disease
Known diseases associated with this structure: Lissencephaly, X-linked OMIM:[300121], Subcortical laminal heteropia, X-linked OMIM:[300121]
About this Structure
2BQQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The DC-module of doublecortin: dynamics, domain boundaries, and functional implications., Cierpicki T, Kim MH, Cooper DR, Derewenda U, Bushweller JH, Derewenda ZS, Proteins. 2006 Sep 1;64(4):874-82. PMID:16835924
Page seeded by OCA on Thu Feb 21 16:40:40 2008
