WD40 repeat explained

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.[1] Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain.

Structure

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).[2] [3] The WD40 domain is composed of several repeats, a variable region of around 20 residues at the beginning followed by a more common repeated set of residues. These 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 7 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.

Function

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.[4] 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.[2] [3]

Examples

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.[5] Human genes encoding proteins containing this domain include:

Human WDR genes and associated diseases
WDR gene other gene names NCBI Entrez
Gene ID 		Human disease associated with mutations
WDR1AIP1; NORI-1; HEL-S-529948
WDR2CORO2A
IR10; CLIPINB
7464
WDR3DIP2; UTP1210885
WDR4TRM82; TRMT8210785
WDR5SWD3; BIG-3; CFAP8911091
WDR611180
WDR7TRAG; KIAA0541; Rabconnectin 3 beta23335
WDR8WRAP7349856
WDR9BRWD1
N143; C21orf107
54014
WDR10IFT122
CED; SPG; CED1; WDR10p; WDR140
55764Sensenbrenner syndrome
WDR11DR11; HH14; BRWD2; WDR1555717Kallmann syndrome
WDR12YTM155759
WDR13MG2164743
WDR14GNB1L
GY2; FKSG1; WDVCF; DGCRK3
54584
WDR15WDR11
WDR16CFAP52
WDRPUH
146845
WDR17116966
WDR18Ipi357418
WDR19ATD5; CED4; DYF-2; ORF26; Oseg6; PWDMP; SRTD5; IFT144; NPHP1357728Sensenbrenner syndrome, Jeune syndrome
WDR20DMR91833
WDR21DCAF4
WDR21A
26094
WDR22DCAF5
BCRG2; BCRP2
8816
WDR23DCAF11
GL014; PRO2389
80344
WDR24JFP7; C16orf2184219
WDR25C14orf6779446
WDR26CDW2; GID7; MIP280232
WDR27253769
WDR28GRWD1; CDW4; GRWD; RRB183743
WDR29SPAG16
PF20
79582
WDR30ATG16L1
IBD10; APG16L; ATG16A; ATG16L
55054Crohn’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
CIA1
9391
WDR40ADCAF12
CT102; TCC52; KIAA1892
25853
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-48
51096
WDR52CFAP4455779
WDR53348793
WDR5484058
WDR5554853
WDR56IFT80
ATD2; SRTD2
57560Jeune syndrome
WDR57SNRNP40
SPF38; PRP8BP; HPRP8BP; PRPF8BP
9410
WDR58THOC6
BBIS; fSAP35
79228
WDR59FP97779726
WDR60SRPS6; SRTD8; FAP16355112Jeune syndrome
WDR61SKI8; REC1480349
WDR62MCPH2; C19orf14284403microcephaly
WDR63DIC3; NYD-SP29126820
WDR64128025
WDR65CFAP57
VWS2
149465Van der Woude syndrome
WDR66CaM-IP4144406
WDR67TBC1D31
Gm85
93594
WDR68DCAF7
AN11; HAN11; SWAN-1
10238
WDR69DAW1
ODA16
164781
WDR7055100
WDR71PAAF1
PAAF; Rpn14
80227
WDR72AI2A3256764Amelogenesis imperfecta
WDR73HSPC26484942
WDR7454663
WDR75NET16; UTP17 84128
WDR76CDW1479968
WDR77p44; MEP50; MEP-50; HKMT1069; Nbla10071; p44/Mep5079084
WDR78DIC479819
WDR79WRAP53
DKCB3; TCAB1
55135
WDR80ATG16L
ATG16B
89849
WDR81CAMRQ2; PPP1R166124997cerebellar ataxia, mental retardation, and dysequilibrium syndrome-2
WDR82SWD2; MST107; WDR82A; MSTP107; PRO2730; TMEM113; PRO3404780335
WDR83MORG184292
WDR84PAK1IP1
PIP1; MAK11
55003
WDR85DPH7
RRT2; C9orf112
92715
WDR86349136
WDR87NYD-SP1183889
WDR88PQWD126248
WDR89MSTP050; C14orf150112840
WDR90C16orf15; C16orf16; C16orf17; C16orf18; C16orf19197335
WDR91HSPC04929062
WDR92MONAD116143
WDR9356964
WDR94AMBRA1
DCAF3
55626
WDR96CFAP43
C10orf79
80217

See also

Notes and References

  1. Neer EJ, Schmidt CJ, Nambudripad R, Smith TF . The ancient regulatory-protein family of WD-repeat proteins . Nature . 371 . 6495 . 297–300 . September 1994 . 8090199 . 10.1038/371297a0 . 1994Natur.371..297N . 600856 .
  2. Smith TF, Gaitatzes C, Saxena K, Neer EJ . The WD40 repeat: a common architecture for diverse functions . Trends Biochem. Sci. . 24 . 5 . 181–5 . May 1999 . 10322433 . 10.1016/S0968-0004(99)01384-5. free .
  3. Li D, Roberts R . WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases . Cell. Mol. Life Sci. . 58 . 14 . 2085–97 . December 2001 . 11814058 . 10.1007/PL00000838. 20646422 .
  4. Stirnimann CU, Petsalaki E, Russell RB, Müller CW . WD40 proteins propel cellular networks. . Trends Biochem. Sci. . 35 . 10 . 565–74 . May 2010 . 20451393 . 10.1016/j.tibs.2010.04.003.
  5. Lander ES, Linton LM, Birren B, etal . Initial sequencing and analysis of the human genome . Nature . 409 . 6822 . 860–921 . February 2001 . 11237011 . 10.1038/35057062 . free .

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