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. Tandem copies of these repeats typically fold together to form a type of circular [2 ] solenoid protein domain called the WD40 domain.
Structure [ edit ]
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 ] 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. [4 ]
Function [ edit ]
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 . The underlying common function of all WD40-repeat proteins is coordinating multi-protein complex assemblies, where the repeating units serve as a rigid [5 ] 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 [ edit ]
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.
Human genes encoding proteins containing this domain include: [6 ]
AAAS, AAMP, AHI1, AMBRA1, APAF1, ARPC1A, ARPC1B, ATG16L1,
BOP1, BRWD1, BRWD2, 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,
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, RAPTOR, 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,
WAIT1, WDF3, WDFY1, WDFY2, WDFY3, WDFY4, WDHD1, WDR1, WDR10, 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,
See also [ edit ]
References [ edit ]
^ ; 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.
^ Neer EJ, Schmidt CJ, Nambudripad R, Smith TF (September 1994). "The ancient regulatory-protein family of WD-repeat proteins". Nature 371 (6495): 297–300. doi: 10.1038/371297a0. PMID 8090199.
^ a b 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.
^ a b 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. PMID 11814058.
^ Stirnimann Christian U, Petsalaki Evangelia, 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.
^ Lander ES, Linton LM, Birren B, et al. (February 2001). "Initial sequencing and analysis of the human genome". Nature 409 (6822): 860–921. doi: 10.1038/35057062. PMID 11237011.
External links [ edit ]
This article incorporates text from the public domain Pfam and InterPro IPR001680