Wikipedia

WD40 repeat

The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide.[2] Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain.

WD domain, G-beta repeat
Ribbon diagram of the C-terminal WD40 domain of Tup1 (a transcriptional corepressor in yeast), which adopts a 7-bladed beta-propeller fold. Ribbon is colored from blue (N-terminus) to red (C-terminus).[1]
Identifiers
SymbolWD40
PfamPF00400
Pfam clanCL0186
InterProIPR001680
PROSITEPDOC00574
SCOP21gp2 / SCOPe / SUPFAM
CDDcd00200
Available protein structures:
PDB  1b9x​, 1b9y​, 1erj​, 1gg2​, 1got​, 1gp2​, 1gxr​, 1nex​, 1nr0​, 1omw​, 1p22​, 1pev​, 1pgu​, 1pi6​, 1s4u​, 1sq9​, 1tbg​, 1u4c​, 1xhm​, 1yfq​, 2bcj​, 2ce8​, 2ce9​, 2trc​ IPR001680 PF00400 (ECOD; PDBsum)  
AlphaFold

Structure

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WD40 domain-containing proteins have 4 to 16 repeating units, all of which are thought to form a circularised beta-propeller structure (see figure to the right).[3][4] The WD40 domain is composed of about 40 to 60[4] amino acids with a glycine and histidine dipeptide near the N-terminus and a tryptophan and aspartic acid dipeptide most commonly at the C-terminus. Two variable regions are present. The repeats typically form a four-stranded anti-parallel beta sheet or blade. These blades come together to form a propeller with the most common being a seven-bladed beta propeller. The blades interlock so that the last beta strand of one repeat forms with the first three of the next repeat to form the 3D blade structure.[3][4]

Function

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WD40-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control, autophagy and apoptosis.[5] The underlying common function of all WD40-repeat proteins is coordinating multi-protein complex assemblies, where the repeating units serve as a rigid scaffold for protein interactions. The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a beta-propeller), TAFII transcription factor, and E3 ubiquitin ligase.[3][4]

Examples

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According to the initial analysis of the human genome WD40 repeats are the eighth largest family of proteins. In all 277 proteins were identified to contain them.[6] Human genes encoding proteins containing this domain include:

Human WDR genes and associated diseases
WDR geneother gene namesNCBI Entrez
Gene ID		Human disease associated with mutations
WDR1AIP1; NORI-1; HEL-S-529948
WDR2CORO2A; IR10; CLIPINB7464
WDR3DIP2; UTP1210885
WDR4TRM82; TRMT8210785
WDR5SWD3; BIG-3; CFAP8911091
WDR611180
WDR7TRAG; KIAA0541; Rabconnectin 3 beta23335
WDR8WRAP7349856
WDR9BRWD1; N143; C21orf10754014
WDR10IFT122; CED; SPG; CED1; WDR10p; WDR14055764Sensenbrenner syndrome
WDR11DR11; HH14; BRWD2; WDR1555717Kallmann syndrome
WDR12YTM155759
WDR13MG2164743
WDR14GNB1L; GY2; FKSG1; WDVCF; DGCRK354584
WDR15WDR11
WDR16CFAP52; WDRPUH146845
WDR17116966
WDR18Ipi357418
WDR19ATD5; CED4; DYF-2; ORF26; Oseg6; PWDMP; SRTD5; IFT144; NPHP1357728Sensenbrenner syndrome, Jeune syndrome
WDR20DMR91833
WDR21DCAF4; WDR21A26094
WDR22DCAF5; BCRG2; BCRP28816
WDR23DCAF11; GL014; PRO238980344
WDR24JFP7; C16orf2184219
WDR25C14orf6779446
WDR26CDW2; GID7; MIP280232
WDR27253769
WDR28GRWD1; CDW4; GRWD; RRB183743
WDR29SPAG16; PF2079582
WDR30ATG16L1; IBD10; APG16L; ATG16A; ATG16L55054Crohn’s disease
WDR31114987
WDR32DCAF1079269
WDR33NET14; WDC14655339
WDR34DIC5; FAP133; SRTD1189891Jeune syndrome
WDR35CED2; IFTA1; SRTD7; IFT12157539Sensenbrenner syndrome
WDR36GLC1G; UTP21; TAWDRP; TA-WDRP134430Primary Open Angle Glaucoma
WDR3722884
WDR38401551
WDR39CIAO1; CIA19391
WDR40ADCAF12; CT102; TCC52; KIAA189225853
WDR41MSTP04855255
WDR43UTP5; NET1223160
WDR44RPH11; RAB11BP54521
WDR45JM5; NBIA4; NBIA5; WDRX1; WIPI4; WIPI-411152Beta-propeller protein-associated neurodegeneration (BPAN)
WDR46UTP7; BING4; FP221; C6orf119277
WDR47NEMITIN; KIAA089322911
WDR48P80; UAF1; SPG6057599
WDR49151790
WDR50UTP18; CGI-4851096
WDR52CFAP4455779
WDR53348793
WDR5484058
WDR5554853
WDR56IFT80; ATD2; SRTD257560Jeune syndrome
WDR57SNRNP40; SPF38; PRP8BP; HPRP8BP; PRPF8BP9410
WDR58THOC6; BBIS; fSAP3579228
WDR59FP97779726
WDR60SRPS6; SRTD8; FAP16355112Jeune syndrome
WDR61SKI8; REC1480349
WDR62MCPH2; C19orf14284403microcephaly
WDR63DIC3; NYD-SP29126820
WDR64128025
WDR65CFAP57; VWS2149465Van der Woude syndrome
WDR66CaM-IP4144406
WDR67TBC1D31; Gm8593594
WDR68DCAF7; AN11; HAN11; SWAN-110238
WDR69DAW1; ODA16164781
WDR7055100
WDR71PAAF1; PAAF; Rpn1480227
WDR72AI2A3256764Amelogenesis imperfecta
WDR73HSPC26484942
WDR7454663
WDR75NET16; UTP1784128
WDR76CDW1479968
WDR77p44; MEP50; MEP-50; HKMT1069; Nbla10071; p44/Mep5079084
WDR78DIC479819
WDR79WRAP53; DKCB3; TCAB155135
WDR80ATG16L; ATG16B89849
WDR81CAMRQ2; PPP1R166124997cerebellar ataxia, mental retardation, and dysequilibrium syndrome-2
WDR82SWD2; MST107; WDR82A; MSTP107; PRO2730; TMEM113; PRO3404780335
WDR83MORG184292
WDR84PAK1IP1; PIP1; MAK1155003
WDR85DPH7; RRT2; C9orf11292715
WDR86349136
WDR87NYD-SP1183889
WDR88PQWD126248
WDR89MSTP050; C14orf150112840
WDR90C16orf15; C16orf16; C16orf17; C16orf18; C16orf19197335
WDR91HSPC04929062
WDR92MONAD116143
WDR9356964
WDR94AMBRA1; DCAF355626
WDR96CFAP43; C10orf7980217

See also

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References

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  1. ↑ PDB: 1erj​; Sprague ER, Redd MJ, Johnson AD, Wolberger C (June 2000). "Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast". EMBO J. 19 (12): 3016–27. doi:10.1093/emboj/19.12.3016. PMC 203344. PMID 10856245.
  2. ↑ Neer EJ, Schmidt CJ, Nambudripad R, Smith TF (September 1994). "The ancient regulatory-protein family of WD-repeat proteins". Nature. 371 (6495): 297–300. Bibcode:1994Natur.371..297N. doi:10.1038/371297a0. PMID 8090199. S2CID 600856.
  3. 1 2 3 Smith TF, Gaitatzes C, Saxena K, Neer EJ (May 1999). "The WD40 repeat: a common architecture for diverse functions". Trends Biochem. Sci. 24 (5): 181–5. doi:10.1016/S0968-0004(99)01384-5. PMID 10322433.
  4. 1 2 3 4 Li D, Roberts R (December 2001). "WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases". Cell. Mol. Life Sci. 58 (14): 2085–97. doi:10.1007/PL00000838. PMC 11337334. PMID 11814058. S2CID 20646422.
  5. ↑ Stirnimann CU, Petsalaki E, Russell RB, Müller CW (May 2010). "WD40 proteins propel cellular networks". Trends Biochem. Sci. 35 (10): 565–74. doi:10.1016/j.tibs.2010.04.003. PMID 20451393.
  6. ↑ Lander ES, Linton LM, Birren B, et al. (February 2001). "Initial sequencing and analysis of the human genome" (PDF). Nature. 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011.
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This article incorporates text from the public domain Pfam and InterPro: IPR001680
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