WD40repeat

The WD40 repeat is a modular protein motif found in many eukaryotic proteins. Named for the conserved tryptophan–aspartic acid (WD) dipeptide that ends most repeats, the motif is about 40 amino acids long. Proteins with multiple WD40 repeats—typically four to eight—fold into a beta-propeller that provides a versatile scaffold for protein–protein interactions.

Structure: Each WD40 repeat contributes one blade of the propeller. Several blades assemble around a central axis to form a circular beta-propeller, usually with four to eight blades. The WD motif and surrounding residues mediate contacts with binding partners; the repeats mainly serve a structural, not catalytic, role.

Function: WD40-repeat proteins act as adaptors or scaffolds in diverse biological processes, including signal transduction, vesicular trafficking, chromatin remodeling, cytoskeletal organization, and transcriptional regulation. They recruit substrates and regulators to larger complexes and can influence ubiquitination or phosphorylation through their interaction surfaces.

Distribution and evolution: WD40 repeats are widespread in eukaryotes. Gene families expanded by duplication and diversification, producing a broad range of domain architectures. While exact repeat sequences vary, the WD motif and the propeller faces show conserved structural features enabling similar interaction surfaces across different proteins.

Examples: Notable WD40-repeat proteins include the beta subunit of heterotrimeric G proteins, DDB1, COP1, and various WD-repeat-containing proteins (WDR family), such as WDR5. The WD40 scaffold is widely used to assemble multiprotein complexes and coordinate signaling networks.