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WD40 Domain
Class:Phospho-Ser/Thr Binding

No ImageThe WD40 repeat region from Cdc4 exhibits eight WD40 repeat regions that form an eight-bladed β-propeller structure. This particular example is unusual in that most of the other WD40 proteins that have been solved show only seven blades. The WD40 domain has been described as a conical frustum with a 40 diameter top surface, a 50 bottom surface, an overall thickness of 30 , and a central pore of 6 diameter. The WD40 domain recognizes the Cdc4 phosphodegron (CPD) peptide using a surface on top surface of the frustum.

Structure Reference:

Orlicky S. et al. (2003) Cell. 112(2): 243-256."WD40 domain of Cdc4 bound to a CPD phosphopeptide from cyclin E". PDB: 1NEX.

Domain binding and function:
WD40 repeats are among the most abundant identifiable protein domains and are found in a wide variety of eukaryotic proteins that have a range of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing, cytoskeleton assembly, gene transcriptional activation and cell cycle control. Among the diversity of WD40 domain function a common theme has emerged that they collude as repeats to form β-propeller structures that acts as a platform for the stable or reversible association of binding partners. The name is derived from the conserved tryptophan and aspartic acid residues and length of approximately 40 amino acids residues that are among the defining characteristics of the repeat. The WD40-repeat domain propeller structure is a versatile module for recognition of post-translational modifications. The WD40-repeat domain of β-TRCP and Cdc4 recognize phosphorylated serine and threonine containing peptides. In contrast, the WD40-repeat domain of WDR5 recognizes a dimethylated lysine peptide in the N-terminal tail of histone H3. 
Examples of Proteins: 
WD40 protein
   Binding partner      Consensus binding motif
βTRCP/Fbw1 β-catenin, IκB    D-pS-G-Φ-X-pS
Cdc4/Fbw7 Cyclin E, Sic1p, Gcn4p

Histone H3

No Image

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