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Function
WD repeat-containing proteins or ribosome biogenesis protein WDR (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 regulators of deubiquinating complexes.
- WD repeat-containing protein 41 is the non-catalytic component of C9orf72-SMCR8 complex which regulates autophagy[3].
- WD repeat-containing protein 55 is a modulator of rRNA synthesis.
- WD repeat-containing protein 61 is a component of PAF1 complex which functions during RNA transcription.
- WD repeat-containing protein 91 functions as negative regulator of the PI3 kinase/PI3K activity in endosomal transport[4].
- WD repeat-containing protein 92 is a modulator of apoptosis.
- WD repeat-containing protein SLP1 is required for mad2-dependent spindle checkpoint activation.
- WD repeat protein CSA or DNA excision repair protein ERCC-8 is part of the transcription-coupled repair complex[5].
Disease
Mutant WDR is involved in triple-A syndrome[6].
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[7]. Water molecules are shown as red spheres.
3D Structures of WD-repeat protein
WD-repeat protein 3D structures
- ↑ 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
- ↑ Sullivan PM, Zhou X, Robins AM, Paushter DH, Kim D, Smolka MB, Hu F. The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. Acta Neuropathol Commun. 2016 May 18;4(1):51. doi: 10.1186/s40478-016-0324-5. PMID:27193190 doi:https://dx.doi.org/10.1186/s40478-016-0324-5
- ↑ Rapiteanu R, Davis LJ, Williamson JC, Timms RT, Paul Luzio J, Lehner PJ. A Genetic Screen Identifies a Critical Role for the WDR81-WDR91 Complex in the Trafficking and Degradation of Tetherin. Traffic. 2016 Aug;17(8):940-58. doi: 10.1111/tra.12409. Epub 2016 May 25. PMID:27126989 doi:https://dx.doi.org/10.1111/tra.12409
- ↑ van der Weegen Y, Golan-Berman H, Mevissen TET, Apelt K, González-Prieto R, Goedhart J, Heilbrun EE, Vertegaal ACO, van den Heuvel D, Walter JC, Adar S, Luijsterburg MS. The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. Nat Commun. 2020 Apr 30;11(1):2104. PMID:32355176 doi:10.1038/s41467-020-15903-8
- ↑ 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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