2h1k
From Proteopedia
(New page: 200px<br /><applet load="2h1k" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h1k, resolution 2.42Å" /> '''Crystal structure of...) |
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| - | [[Image:2h1k.gif|left|200px]]<br /><applet load="2h1k" size=" | + | [[Image:2h1k.gif|left|200px]]<br /><applet load="2h1k" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2h1k, resolution 2.42Å" /> | caption="2h1k, resolution 2.42Å" /> | ||
'''Crystal structure of the Pdx1 homeodomain in complex with DNA'''<br /> | '''Crystal structure of the Pdx1 homeodomain in complex with DNA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription | + | Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belonging to the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell development and maintenance of adult islet beta-cell function. Mutations in the human pdx1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus, MODY-4. We demonstrate that the homeodomain reproduces the binding specificity of the full-length protein. We report the 2.4 A resolution crystal structure of the homeodomain bound to a target DNA. The two Pdx1/DNA complexes in the asymmetric unit display conformational differences: in the DNA curvature, the orientation of the homeodomain in the major groove, and the order of the N-terminal arm. Comparing the two complexes indicates invariant protein-DNA contacts, and variant contacts that are unique to each binding orientation. An induced fit model is proposed that depends on the DNA conformation and provides a mechanism for nonlocal contributions to binding specificity. |
==About this Structure== | ==About this Structure== | ||
| - | 2H1K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus]. Full crystallographic information is available from [http:// | + | 2H1K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H1K OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis for induced fit mechanisms in DNA recognition by the | + | Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain., Longo A, Guanga GP, Rose RB, Biochemistry. 2007 Mar 20;46(11):2948-57. Epub 2007 Feb 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17315980 17315980] |
[[Category: Mesocricetus auratus]] | [[Category: Mesocricetus auratus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Guanga, G | + | [[Category: Guanga, G P.]] |
[[Category: Longo, A.]] | [[Category: Longo, A.]] | ||
| - | [[Category: Rose, R | + | [[Category: Rose, R B.]] |
[[Category: protein-dna complex]] | [[Category: protein-dna complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:17 2008'' |
Revision as of 15:37, 21 February 2008
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Crystal structure of the Pdx1 homeodomain in complex with DNA
Overview
Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belonging to the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell development and maintenance of adult islet beta-cell function. Mutations in the human pdx1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus, MODY-4. We demonstrate that the homeodomain reproduces the binding specificity of the full-length protein. We report the 2.4 A resolution crystal structure of the homeodomain bound to a target DNA. The two Pdx1/DNA complexes in the asymmetric unit display conformational differences: in the DNA curvature, the orientation of the homeodomain in the major groove, and the order of the N-terminal arm. Comparing the two complexes indicates invariant protein-DNA contacts, and variant contacts that are unique to each binding orientation. An induced fit model is proposed that depends on the DNA conformation and provides a mechanism for nonlocal contributions to binding specificity.
About this Structure
2H1K is a Single protein structure of sequence from Mesocricetus auratus. Full crystallographic information is available from OCA.
Reference
Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain., Longo A, Guanga GP, Rose RB, Biochemistry. 2007 Mar 20;46(11):2948-57. Epub 2007 Feb 23. PMID:17315980
Page seeded by OCA on Thu Feb 21 17:37:17 2008
