WD40 repeat

Last updated
WD domain, G-beta repeat
1erj 7bladed beta propeller.png
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
Pfam PF00400
Pfam clan CL0186
InterPro IPR001680
PROSITE PDOC00574
SCOP2 1gp2 / SCOPe / SUPFAM
CDD cd00200

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.

Contents

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). [3] [4] 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. [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

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
WDR1 AIP1; NORI-1; HEL-S-529948
WDR2 CORO2A; IR10; CLIPINB7464
WDR3 DIP2; UTP1210885
WDR4 TRM82; TRMT8210785
WDR5 SWD3; BIG-3; CFAP8911091
WDR6 11180
WDR7 TRAG; KIAA0541; Rabconnectin 3 beta23335
WDR8 WRAP73 49856
WDR9 BRWD1; N143; C21orf10754014
WDR10 IFT122; CED; SPG; CED1; WDR10p; WDR14055764 Sensenbrenner syndrome
WDR11 DR11; HH14; BRWD2; WDR1555717 Kallmann syndrome
WDR12 YTM155759
WDR13 MG2164743
WDR14 GNB1L; GY2; FKSG1; WDVCF; DGCRK354584
WDR15 WDR11
WDR16 CFAP52; WDRPUH146845
WDR17 116966
WDR18 Ipi357418
WDR19 ATD5; CED4; DYF-2; ORF26; Oseg6; PWDMP; SRTD5; IFT144; NPHP1357728 Sensenbrenner syndrome, Jeune syndrome
WDR20 DMR91833
WDR21 DCAF4; WDR21A26094
WDR22 DCAF5; BCRG2; BCRP28816
WDR23 DCAF11; GL014; PRO238980344
WDR24 JFP7; C16orf2184219
WDR25 C14orf6779446
WDR26 CDW2; GID7; MIP280232
WDR27 253769
WDR28 GRWD1; CDW4; GRWD; RRB183743
WDR29 SPAG16; PF2079582
WDR30 ATG16L1; IBD10; APG16L; ATG16A; ATG16L55054 Crohn’s disease
WDR31 114987
WDR32 DCAF10 79269
WDR33 NET14; WDC14655339
WDR34 DIC5; FAP133; SRTD1189891 Jeune syndrome
WDR35 CED2; IFTA1; SRTD7; IFT12157539 Sensenbrenner syndrome
WDR36 GLC1G; UTP21; TAWDRP; TA-WDRP134430 Primary Open Angle Glaucoma
WDR37 22884
WDR38 401551
WDR39 CIAO1; CIA19391
WDR40A DCAF12; CT102; TCC52; KIAA189225853
WDR41 MSTP04855255
WDR43 UTP5; NET1223160
WDR44 RPH11; RAB11BP54521
WDR45 JM5; NBIA4; NBIA5; WDRX1; WIPI4; WIPI-411152 Beta-propeller protein-associated neurodegeneration (BPAN)
WDR46 UTP7; BING4; FP221; C6orf119277
WDR47 NEMITIN; KIAA089322911
WDR48 P80; UAF1; SPG6057599
WDR49 151790
WDR50 UTP18; CGI-4851096
WDR52 CFAP44 55779
WDR53 348793
WDR54 84058
WDR55 54853
WDR56 IFT80; ATD2; SRTD257560 Jeune syndrome
WDR57 SNRNP40; SPF38; PRP8BP; HPRP8BP; PRPF8BP9410
WDR58 THOC6; BBIS; fSAP3579228
WDR59 FP97779726
WDR60 SRPS6; SRTD8; FAP16355112 Jeune syndrome
WDR61 SKI8; REC1480349
WDR62 MCPH2; C19orf14284403 microcephaly
WDR63 DIC3; NYD-SP29126820
WDR64 128025
WDR65 CFAP57; VWS2149465 Van der Woude syndrome
WDR66 CaM-IP4144406
WDR67 TBC1D31; Gm8593594
WDR68 DCAF7; AN11; HAN11; SWAN-110238
WDR69 DAW1; ODA16164781
WDR70 55100
WDR71 PAAF1; PAAF; Rpn1480227
WDR72 AI2A3256764 Amelogenesis imperfecta
WDR73 HSPC26484942
WDR74 54663
WDR75 NET16; UTP1784128
WDR76 CDW1479968
WDR77 p44; MEP50; MEP-50; HKMT1069; Nbla10071; p44/Mep5079084
WDR78 DIC479819
WDR79 WRAP53; DKCB3; TCAB155135
WDR80 ATG16L; ATG16B89849
WDR81 CAMRQ2; PPP1R166124997 cerebellar ataxia, mental retardation, and dysequilibrium syndrome-2
WDR82 SWD2; MST107; WDR82A; MSTP107; PRO2730; TMEM113; PRO3404780335
WDR83 MORG184292
WDR84 PAK1IP1; PIP1; MAK1155003
WDR85 DPH7; RRT2; C9orf11292715
WDR86 349136
WDR87 NYD-SP1183889
WDR88 PQWD126248
WDR89 MSTP050; C14orf150112840
WDR90 C16orf15; C16orf16; C16orf17; C16orf18; C16orf19197335
WDR91 HSPC04929062
WDR92 MONAD116143
WDR93 56964
WDR94 AMBRA1; DCAF355626
WDR96 CFAP43; C10orf7980217

See also

Related Research Articles

<span class="mw-page-title-main">SH3 domain</span> Small protein domain found in some kinases and GTPases

The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.

<span class="mw-page-title-main">14-3-3 protein</span> Family of conserved regulatory molecules

14-3-3 proteins are a family of conserved regulatory molecules that are expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. More than 200 signaling proteins have been reported as 14-3-3 ligands.

A nuclear localization signalorsequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus.

<span class="mw-page-title-main">Ankyrin repeat</span>

The ankyrin repeat is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and Drosophila Notch. Domains consisting of ankyrin tandem repeats mediate protein–protein interactions and are among the most common structural motifs in known proteins. They appear in bacterial, archaeal, and eukaryotic proteins, but are far more common in eukaryotes. Ankyrin repeat proteins, though absent in most viruses, are common among poxviruses. Most proteins that contain the motif have four to six repeats, although its namesake ankyrin contains 24, and the largest known number of repeats is 34, predicted in a protein expressed by Giardia lamblia.

<span class="mw-page-title-main">Armadillo repeat</span>

An armadillo repeat is the name of a characteristic, repetitive amino acid sequence of about 40 residues in length that is found in many proteins. Proteins that contain armadillo repeats typically contain several tandemly repeated copies. Each armadillo repeat is composed of a pair of alpha helices that form a hairpin structure. Multiple copies of the repeat form what is known as an alpha solenoid structure.

<span class="mw-page-title-main">Leucine-rich repeat</span>

A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats commonly fold together to form a solenoid protein domain, termed leucine-rich repeat domain. Typically, each repeat unit has beta strand-turn-alpha helix structure, and the assembled domain, composed of many such repeats, has a horseshoe shape with an interior parallel beta sheet and an exterior array of helices. One face of the beta sheet and one side of the helix array are exposed to solvent and are therefore dominated by hydrophilic residues. The region between the helices and sheets is the protein's hydrophobic core and is tightly sterically packed with leucine residues.

<span class="mw-page-title-main">FBXW7</span>

F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.

<span class="mw-page-title-main">FBXW11</span>

βTrCP2 is a protein that in humans is encoded by the FBXW11 gene.

<span class="mw-page-title-main">FBXW2</span> Protein-coding gene in the species Homo sapiens

F-box/WD repeat-containing protein 2 is a protein that in humans is encoded by the FBXW2 gene.

<span class="mw-page-title-main">FBXW5</span> Protein-coding gene in the species Homo sapiens

F-box/WD repeat-containing protein 5 is a protein that in humans is encoded by the FBXW5 gene.

Coronin is an actin binding protein which also interacts with microtubules and in some cell types is associated with phagocytosis. Coronin proteins are expressed in a large number of eukaryotic organisms from yeast to humans.

<span class="mw-page-title-main">Inhibitor of apoptosis domain</span>

The inhibitor of apoptosis domain -- also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR -- is a structural motif found in proteins with roles in apoptosis, cytokine production, and chromosome segregation. Proteins containing BIR are known as inhibitor of apoptosis proteins (IAPs), or BIR-containing proteins, and include BIRC1 (NAIP), BIRC2 (cIAP1), BIRC3 (cIAP2), BIRC4 (xIAP), BIRC5 (survivin) and BIRC6.

<span class="mw-page-title-main">Tetratricopeptide repeat</span> Protein tandem repeat

The tetratricopeptide repeat (TPR) is a structural motif. It consists of a degenerate 34 amino acid tandem repeat identified in a wide variety of proteins. It is found in tandem arrays of 3–16 motifs, which form scaffolds to mediate protein–protein interactions and often the assembly of multiprotein complexes. These alpha-helix pair repeats usually fold together to produce a single, linear solenoid domain called a TPR domain. Proteins with such domains include the anaphase-promoting complex (APC) subunits cdc16, cdc23 and cdc27, the NADPH oxidase subunit p67-phox, hsp90-binding immunophilins, transcription factors, the protein kinase R (PKR), the major receptor for peroxisomal matrix protein import PEX5, protein arginine methyltransferase 9 (PRMT9), and mitochondrial import proteins.

WDR75 is a human protein encoded by the WDR75 gene containing a WD40 superfamily domain. The WD40 domain is found throughout many eukaryotic cell types and is known to be involved in cellular regulator functions such as pre-mRNA processing and cytoskeleton assembly. The function of the WDR75 protein is not defined by the scientific community.

<span class="mw-page-title-main">Kelch motif</span>

The Kelch motif is a region of protein sequence found widely in proteins from bacteria and eukaryotes. This sequence motif is composed of about 50 amino acid residues which form a structure of a four stranded beta-sheet "blade". This sequence motif is found in between five and eight tandem copies per protein which fold together to form a larger circular solenoid structure called a beta-propeller domain.

<span class="mw-page-title-main">BRCT domain</span>

BRCA1 C Terminus (BRCT) domain is a family of evolutionarily related proteins. It is named after the C-terminal domain of BRCA1, a DNA-repair protein that serves as a marker of breast cancer susceptibility.

WH1 domain is an evolutionary conserved protein domain. Therefore, it has an important function.

<span class="mw-page-title-main">Forkhead-associated domain</span>

In molecular biology, the forkhead-associated domain is a phosphopeptide recognition domain found in many regulatory proteins. It displays specificity for phosphothreonine-containing epitopes but will also recognise phosphotyrosine with relatively high affinity. It spans approximately 80-100 amino acid residues folded into an 11-stranded beta sandwich, which sometimes contains small helical insertions between the loops connecting the strands.

<span class="mw-page-title-main">Eukaryotic translation initiation factor 4E family</span>

In molecular biology, the eukaryotic translation initiation factor 4E family (eIF-4E) is a family of proteins that bind to the cap structure of eukaryotic cellular mRNAs. Members of this family recognise and bind the 7-methyl-guanosine-containing (m7Gppp) cap during an early step in the initiation of protein synthesis and facilitate ribosome binding to an mRNA by inducing the unwinding of its secondary structures. A tryptophan in the central part of the sequence of human eIF-4E seems to be implicated in cap-binding.

Clathrin adaptor proteins, also known as adaptins, are vesicular transport adaptor proteins associated with clathrin. These proteins are synthesized in the ribosomes, processed in the endoplasmic reticulum and transported from the Golgi apparatus to the trans-Golgi network, and from there via small carrier vesicles to their final destination compartment. The association between adaptins and clathrin are important for vesicular cargo selection and transporting. Clathrin coats contain both clathrin and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Therefore, adaptor proteins are responsible for the recruitment of cargo molecules into a growing clathrin-coated pits. The two major types of clathrin adaptor complexes are the heterotetrameric vesicular transport adaptor proteins (AP1-5), and the monomeric GGA adaptors. Adaptins are distantly related to the other main type of vesicular transport proteins, the coatomer subunits, sharing between 16% and 26% of their amino acid sequence.

References

  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 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 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. 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.
This article incorporates text from the public domain Pfam and InterPro: IPR001680