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3n0d

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Revision as of 09:36, 25 December 2014

Crystal structure of WDR5 mutant (W330F)

Structural highlights

3n0d is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3mxx, 3n0e
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[WDR5_HUMAN] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

We recently found that Asp-His-Ser/Thr-Trp hydrogen-bonded tetrads are widely and uniquely present in the WD40-repeat proteins. WDR5 protein is a seven WD40-repeat propeller with five such tetrads. To explore the effect of the tetrad on the structure and stability of WD40-repeat proteins, the wild-type WDR5 and its seven mutants involving the substitutions of tetrad residues have been isolated. The crystal structures of the wild-type WDR5 and its three WDR5 mutants have been determined by X-ray diffraction method. The mutations of the tetrad residues are found not to change the basic structural features. The denaturing profiles of the wild type and the seven mutants with the use of denaturant guanidine hydrochloride have been studied by circular dichroism spectroscopy to determine the folding free energies of these proteins. The folding free energies of the wild type and the S62A, S146A, S188A, D192E, W330F, W330Y, and D324E mutants are measured to be about -11.6, -2.7, -3.1, -2.9, -3.6, -7.1, -7.0, and -7.5 kcal/mol, respectively. These suggest that (1) the hydrogen bonds in these hydrogen bond networks are unusually strong; (2) each hydrogen-bonded tetrad provides over 12 kcal/mol stability to the protein; thus, the removal of any single tetrad would cause unfolding of the protein; (3) since there are five tetrads, the protein must be in a highly unstable state without the tetrads, which might be related to its biological functions.

The Effect of Asp-His-Ser/Thr-Trp Tetrad on the Thermostability of WD40-Repeat Proteins.,Wu XH, Chen RC, Gao Y, Wu YD Biochemistry. 2010 Nov 30;49(47):10237-45. Epub 2010 Nov 8. PMID:20939513^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Patel A, Dharmarajan V, Vought VE, Cosgrove MS. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2009 Sep 4;284(36):24242-56. Epub 2009 Jun 25. PMID:19556245 doi:M109.014498
↑ Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009 Mar;29(5):1176-88. doi: 10.1128/MCB.01599-08. Epub 2008 Dec, 22. PMID:19103755 doi:10.1128/MCB.01599-08
↑ Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010 Feb 12;285(7):4268-72. doi: 10.1074/jbc.C109.087981. Epub 2009 , Dec 14. PMID:20018852 doi:10.1074/jbc.C109.087981
↑ Han Z, Guo L, Wang H, Shen Y, Deng XW, Chai J. Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol Cell. 2006 Apr 7;22(1):137-44. PMID:16600877 doi:10.1016/j.molcel.2006.03.018
↑ Couture JF, Collazo E, Trievel RC. Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol. 2006 Aug;13(8):698-703. Epub 2006 Jul 9. PMID:16829960 doi:10.1038/nsmb1116
↑ Wu XH, Chen RC, Gao Y, Wu YD. The Effect of Asp-His-Ser/Thr-Trp Tetrad on the Thermostability of WD40-Repeat Proteins. Biochemistry. 2010 Nov 30;49(47):10237-45. Epub 2010 Nov 8. PMID:20939513 doi:10.1021/bi101321y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3n0d"

@@ Line 6: / Line 6: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n0d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n0d RCSB], [http://www.ebi.ac.uk/pdbsum/3n0d PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3n0d

From Proteopedia

Revision as of 09:36, 25 December 2014

Crystal structure of WDR5 mutant (W330F)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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