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| - | [[Image:2jp9.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2jp9| PDB=2jp9 | SCENE= }} | | {{STRUCTURE_2jp9| PDB=2jp9 | SCENE= }} |
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| - | '''Structure of the Wilms Tumor Suppressor Protein Zinc Finger Domain Bound to DNA'''
| + | ===Structure of the Wilms Tumor Suppressor Protein Zinc Finger Domain Bound to DNA=== |
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| - | ==Overview==
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| - | The zinc finger domain of the Wilms tumor suppressor protein (WT1) contains four canonical Cys(2)His(2) zinc fingers. WT1 binds preferentially to DNA sequences that are closely related to the EGR-1 consensus site. We report the structure determination by both X-ray crystallography and NMR spectroscopy of the WT1 zinc finger domain in complex with DNA. The X-ray structure was determined for the complex with a cognate 14 base-pair oligonucleotide, and composite X-ray/NMR structures were determined for complexes with both the 14 base-pair and an extended 17 base-pair DNA. This combined approach allowed unambiguous determination of the position of the first zinc finger, which is influenced by lattice contacts in the crystal structure. The crystal structure shows the second, third and fourth zinc finger domains inserted deep into the major groove of the DNA where they make base-specific interactions. The DNA duplex is distorted in the vicinity of the first zinc finger, with a cytidine twisted and tilted out of the base stack to pack against finger 1 and the tip of finger 2. By contrast, the composite X-ray/NMR structures show that finger 1 continues to follow the major groove in the solution complexes. However, the orientation of the helix is non-canonical, and the fingertip and the N terminus of the helix project out of the major groove; as a consequence, the zinc finger side-chains that are commonly involved in base recognition make no contact with the DNA. We conclude that finger 1 helps to anchor WT1 to the DNA by amplifying the binding affinity although it does not contribute significantly to binding specificity. The structures provide molecular level insights into the potential consequences of mutations in zinc fingers 2 and 3 that are associated with Denys-Drash syndrome and nephritic syndrome. The mutations are of two types, and either destabilize the zinc finger structure or replace key base contact residues. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17716689}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17716689 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17716689}} |
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| | ==Disease== | | ==Disease== |
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| | ==About this Structure== | | ==About this Structure== |
| - | 2JP9 is a [[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=2JP9 OCA]. | + | 2JP9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JP9 OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Zinc finger]] | | [[Category: Zinc finger]] |
| | [[Category: Zinc-finger]] | | [[Category: Zinc-finger]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:08:38 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:01:50 2008'' |
Revision as of 11:01, 28 July 2008
Template:STRUCTURE 2jp9
Structure of the Wilms Tumor Suppressor Protein Zinc Finger Domain Bound to DNA
Template:ABSTRACT PUBMED 17716689
Disease
Known disease associated with this structure: Denys-Drash syndrome OMIM:[607102], Frasier syndrome OMIM:[607102], Mesangial sclerosis, isolated diffuse OMIM:[607102], WAGR syndrome OMIM:[607102], Wilms tumor, type 1 OMIM:[607102]
About this Structure
2JP9 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.
Reference
Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA., Stoll R, Lee BM, Debler EW, Laity JH, Wilson IA, Dyson HJ, Wright PE, J Mol Biol. 2007 Oct 5;372(5):1227-45. Epub 2007 Jul 21. PMID:17716689
Page seeded by OCA on Mon Jul 28 14:01:50 2008
