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| <StructureSection load='2h9m' size='340' side='right' caption='Human WD-repeat protein 5 (grey) complex with histone H3 peptide (green) (PDB code [[2h9m]])'> | | <StructureSection load='2h9m' size='340' side='right' caption='Human WD-repeat protein 5 (grey) complex with histone H3 peptide (green) (PDB code [[2h9m]])'> |
| == Function == | | == Function == |
| '''WD-repeat protein 5''' (WDR5) contains 7 WD repeats. WD repeats are ca. 40 amino acid long usually bordered by Gly-His and Trp-Asp (WD). WDR5 contributes to histone modification. It may position the N-terminal of histone H3 for efficient methylation at Lys4. This methylation is implicated in the control of activation of cell lineage genes during embryogenesis. WDR5 interacts with histone-lysine N-methyltransferase (MLL)<ref>PMID:21531708</ref>. WDR5 forms a beta propeller structure. | | '''WD repeat-containing proteins''' (WDR) contain 4 or more repeating WD units. WD repeats are ca. 40 amino acid long usually bordered by Gly-His and Trp-Asp (WD). All WDRs form a β-propeller structure. WDRs have critical roles in many biological functions like signal transduction, transcription regulation and apoptosis<ref>PMID:11814058</ref>. <br /> |
| | *'''WD-repeat protein 5''' (WDR5) contains 7 WD repeats. WDR5 contributes to histone modification. It may position the N-terminal of histone H3 for efficient methylation at Lys4. This methylation is implicated in the control of activation of cell lineage genes during embryogenesis. WDR5 interacts with histone-lysine N-methyltransferase (MLL)<ref>PMID:21531708</ref>. <br /> |
| | *'''WD repeat-containing protein 48 and 20''' act as regulator of deubiquinating complexes. |
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| == Disease == | | == Disease == |
Revision as of 09:36, 14 December 2016
| Function
WD repeat-containing proteins (WDR) contain 4 or more repeating WD units. WD repeats are ca. 40 amino acid long usually bordered by Gly-His and Trp-Asp (WD). All WDRs form a β-propeller structure. WDRs have critical roles in many biological functions like signal transduction, transcription regulation and apoptosis[1].
- WD-repeat protein 5 (WDR5) contains 7 WD repeats. WDR5 contributes to histone modification. It may position the N-terminal of histone H3 for efficient methylation at Lys4. This methylation is implicated in the control of activation of cell lineage genes during embryogenesis. WDR5 interacts with histone-lysine N-methyltransferase (MLL)[2].
- WD repeat-containing protein 48 and 20 act as regulator of deubiquinating complexes.
Disease
Mutant WDR is involved in triple-A syndrome[3].
Structural highlights
The histone Arg2 residue inserts into the central pore of the WDR5 β-propellor structure acting like an anchoring pin forming numerous hydrogen bonds and cation-π interactions[4].
- ↑ Li D, Roberts R. WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases. Cell Mol Life Sci. 2001 Dec;58(14):2085-97. PMID:11814058
- ↑ Gan Q, Thiebaud P, Theze N, Jin L, Xu G, Grant P, Owens GK. WD repeat-containing protein 5, a ubiquitously expressed histone methyltransferase adaptor protein, regulates smooth muscle cell-selective gene activation through interaction with pituitary homeobox 2. J Biol Chem. 2011 Jun 17;286(24):21853-64. doi: 10.1074/jbc.M111.233098. Epub, 2011 Apr 28. PMID:21531708 doi:https://dx.doi.org/10.1074/jbc.M111.233098
- ↑ Tullio-Pelet A, Salomon R, Hadj-Rabia S, Mugnier C, de Laet MH, Chaouachi B, Bakiri F, Brottier P, Cattolico L, Penet C, Begeot M, Naville D, Nicolino M, Chaussain JL, Weissenbach J, Munnich A, Lyonnet S. Mutant WD-repeat protein in triple-A syndrome. Nat Genet. 2000 Nov;26(3):332-5. PMID:11062474 doi:https://dx.doi.org/10.1038/81642
- ↑ Schuetz A, Allali-Hassani A, Martin F, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Arrowsmith CH, Min J. Structural basis for molecular recognition and presentation of histone H3 by WDR5. EMBO J. 2006 Sep 20;25(18):4245-52. Epub 2006 Aug 31. PMID:16946699
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3D Structures of WD-repeat protein 5
Updated on 14-December-2016
{"openlevels":0}
- WDR5
- 2gnq, 2h68, 2h14, 2h9l – hWDR5 – human
- [3mxx]], 3n0d, 3n0e – hWDR5 (mutant)
- 3smr, 3ur4, 4ia9, 4qqe, 4ql1, 5eal, 5eam, 5eap, 5ear – hWDR5 + piperazine derivative
- 2cnx, 2co0, 2h6k, 2h6n, 2h6q, 2h13, 2h9m, 2h9n, 2h9p, 2g99, 2g9a, 2o9k, 3psl, 4a7j – hWDR5 + histone H3 peptide
- 3eg6, 3emh – hWDR5 + MLL1 peptide
- 4gm3, 4gm8, 4gm9, 4gmb – hWDR5 + peptide inhibitor
- 2xl2, 2xl3 – hWDR5 + retinoblastoma-binding protein 5 peptide
- 4o45 – hWDR5 + influenza NS1 C-terminal
- 4cy1 – hWDR5 + KAT8 regulatory NSL complex subunit 1+2 peptides
- 4cy2 – hWDR5 + KAT8 regulatory NSL complex subunit 1 peptide
- 4y7r – hWDR5 + Myc MbIIIb peptide
- 3uvk, 3uvl, 3uvm, 3uvn, 3uvo, 4erq, 4ery, 4es0, 4esg, 4ewr, 5sxm – hWDR5 + MLL peptide
- 4erz – hWDR5 + MLL4
- 3p4f – hWDR5 + retinoblastoma-binding protein 5 peptide + MLL peptide
- WDR20
- WDR48
- 5cvl – hWDR48
- 5l8e – hWDR48 + peptide
- 5l8w, 5cvn, 5cvo – hWDR48 + ubiquitin + ubiquitin carboxyl-terminal hydrolase
- 5k1a, 5k1b – hWDR48 + ubiquitin carboxyl-terminal hydrolase
- 5k1c – hWDR48 + WDR20 + ubiquitin carboxyl-terminal hydrolase
References
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