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 about 40 to 60^[3] 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.^{[2] [3]}

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:

• AAAS, AAMP, AHI1, AMBRA1, APAF1, ARPC1A, ARPC1B, ATG16L1,
• BOP1, BRWD1, BRWD3, BTRC, BUB3,
• C6orf11, CDC20, CDC40, CDRT1, CHAF1B, CIAO1, CIRH1A, COPA, COPB2, CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO6, CORO7, CSTF1,
• DDB2, DENND3, DMWD, DMXL1, DMXL2, DNAI1, DNAI2, DNCI1, DTL, DYNC1I1, DYNC1I2, EDC4,
• EED, EIF3S2, ELP2, EML1, EML2, EML3, EML4, EML4-ALK, EML5, ERCC8,
• FBXW10, FBXW11, FBXW2, FBXW4, FBXW5, FBXW7, FBXW8, FBXW9, FZR1,
• GBL, GEMIN5, GNB1, GNB1L, GNB2, GNB2L1, GNB3, GNB4, GNB5, GRWD1, GTF3C2,
• HERC1, HIRA, HZGJ,
• IFT121, IFT122, IFT140, IFT172, IFT80, IQWD1,
• KATNB1, KIAA1336, KIF21A, KIF21B, KM-PA-2,
• KEAP1,
• LLGL1, LLGL2, LRBA, LRRK1, LRRK2, LRWD1, LYST,
• MAPKBP1, MED16, MORG1,
• NBEA, NBEAL1, NEDD1, NLE1, NSMAF, NUP37, NUP43, NWD1,
• PAAF1, PAFAH1B1, PAK1IP1, PEX7, PHIP, PIK3R4, PLAA, PLRG1, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R2D, PPWD1, PREB, PRPF19, PRPF4, PWP1, PWP2,
• RAE1, RPTOR, RBBP4, RBBP5, RBBP7, RFWD2, RFWD3, RRP9,
• SCAP, SEC13, SEC31A, SEC31B, SEH1L, SHKBP1, SMU1, SPAG16, SPG, STRAP, STRN, STRN3, STRN4, STXBP5, STXBP5L,
• TAF5, TAF5L, TBL1X, TBL1XR1, TBL1Y, TBL2, TBL3, TEP1, THOC3, THOC6, TLE1, TLE2, TLE3, TLE4, TLE6, TRAF7, TSSC1, TULP4, TUWD12,
• UTP15, UTP18,
• WAIT1, WDF3, WDFY1, WDFY2, WDFY3, WDFY4, WDHD1, WDR1, WDR10, WDR11, WDR12, WDR13, WDR16, WDR17, WDR18, WDR19, WDR20, WDR21A, WDR21C, WDR22, WDR23, WDR24, WDR25, WDR26, WDR27, WDR3, WDR31, WDR32, WDR33, WDR34, WDR35, WDR36, WDR37, WDR38, WDR4, WDR40A, WDR40B, WDR40C, WDR41, WDR42A, WDR42B, WDR43, WDR44, WDR46, WDR47, WDR48, WDR49, WDR5, WDR51A, WDR51B, WDR52, WDR53, WDR54, WDR55, WDR57, WDR59, WDR5B, WDR6, WDR60, WDR61, WDR62, WDR63, WDR64, WDR65, WDR66, WDR67, WDR68, WDR69, WDR7, WDR70, WDR72, WDR73, WDR74, WDR75, WDR76, WDR77, WDR78, WDR79, WDR8, WDR81, WDR82, WDR85, WDR86, WDR88, WDR89, WDR90, WDR91, WDR92, WDSOF1, WDSUB1, WDTC1, WSB1, WSB2,
• ZFP106

See also

• Beta-propeller
• Tomosyn, a protein two WD40 domains
• Protein tandem repeats

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 . 11337334 .
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 .