2h14
From Proteopedia
(New page: 200px<br /> <applet load="2h14" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h14, resolution 1.48Å" /> '''Crystal of WDR5 (ap...) |
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| - | [[Image:2h14.gif|left|200px]]<br /> | + | [[Image:2h14.gif|left|200px]]<br /><applet load="2h14" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2h14" size=" | + | |
caption="2h14, resolution 1.48Å" /> | caption="2h14, resolution 1.48Å" /> | ||
'''Crystal of WDR5 (apo-form)'''<br /> | '''Crystal of WDR5 (apo-form)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) | + | The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) histone methyltransferase complexes. WDR5 has been reported to selectively bind dimethylated Lys4 (K4me2) in histone H3 to promote K4 trimethylation by TRX. To elucidate the basis of this binding specificity, we have determined the crystal structure of WDR5 bound to a histone H3 peptide bearing K4me2. The structure reveals that the N terminus of histone H3 binds as a 3(10)-helix in the central depression formed by the WD40 repeats. R2 in histone H3 is bound in the acidic channel in the protein's core, whereas K4me2 is solvent exposed and does not engage in direct interactions with WDR5. Functional studies confirm that WDR5 recognizes A1, R2 and T3 in histone H3 but has virtually identical affinities for the unmodified and mono-, di- and trimethylated forms of K4, demonstrating that it does not discriminate among different degrees of methylation of this residue. |
==Disease== | ==Disease== | ||
| - | Known disease associated with this structure: Asphyxiating thoracic dystrophy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611177 611177]] | + | Known disease associated with this structure: Asphyxiating thoracic dystrophy 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611177 611177]] |
==About this Structure== | ==About this Structure== | ||
| - | 2H14 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:// | + | 2H14 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=2H14 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Collazo, E.]] | [[Category: Collazo, E.]] | ||
| - | [[Category: Couture, J | + | [[Category: Couture, J F.]] |
| - | [[Category: Trievel, R | + | [[Category: Trievel, R C.]] |
[[Category: beta-propeller]] | [[Category: beta-propeller]] | ||
[[Category: histone]] | [[Category: histone]] | ||
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[[Category: wd-40 repeats]] | [[Category: wd-40 repeats]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:37:07 2008'' |
Revision as of 15:37, 21 February 2008
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Crystal of WDR5 (apo-form)
Contents |
Overview
The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) histone methyltransferase complexes. WDR5 has been reported to selectively bind dimethylated Lys4 (K4me2) in histone H3 to promote K4 trimethylation by TRX. To elucidate the basis of this binding specificity, we have determined the crystal structure of WDR5 bound to a histone H3 peptide bearing K4me2. The structure reveals that the N terminus of histone H3 binds as a 3(10)-helix in the central depression formed by the WD40 repeats. R2 in histone H3 is bound in the acidic channel in the protein's core, whereas K4me2 is solvent exposed and does not engage in direct interactions with WDR5. Functional studies confirm that WDR5 recognizes A1, R2 and T3 in histone H3 but has virtually identical affinities for the unmodified and mono-, di- and trimethylated forms of K4, demonstrating that it does not discriminate among different degrees of methylation of this residue.
Disease
Known disease associated with this structure: Asphyxiating thoracic dystrophy 2 OMIM:[611177]
About this Structure
2H14 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular recognition of histone H3 by the WD40 protein WDR5., Couture JF, Collazo E, Trievel RC, Nat Struct Mol Biol. 2006 Aug;13(8):698-703. Epub 2006 Jul 9. PMID:16829960
Page seeded by OCA on Thu Feb 21 17:37:07 2008
