WD40-Protein Repeats

The WD40 domain is one of the most abundant and interacting domains in the eukaryotic genome. The conserved tryptophan aspartic acid (WD) motif and the length of 40 are conventionally adopted to name the repeats and the domains. The proteins that contain a WD40 domain- represent one of the most abundant protein families in eukaryotes. They often serve as scaffolds in the assembly of functional complexes by interaction with other macromolecules.

A typical WD40 domain consists of a propeller-like structure composed of 7 repeating blades, each containing 40-60 residues and folded into four antiparallel β-strands. WD40 lamellae exhibit two predominant structural motifs, one of which is the stability-promoting side-chain hydrogen-bonding network formed by residues of aspartic acid, histidine, serine (or threonine), and tryptophan (DH[S/T]W, or tetrad).

The WD40 domain structure provides a platform for the interaction and assembly of multiple proteins into a signalosome. WD40 repeat-containing proteins are mainly involved in growth, cell cycle, development, and virulence in lower eukaryotes, whereas in higher organisms they play important roles in various cellular functions such as signal transduction, cell cycle control, intracellular transport, chromatin remodeling, cytoskeletal organization, apoptosis, development, transcriptional regulation, and immune response. To play the regulatory role in various processes, they act as scaffolds for protein-protein or protein-DNA interactions.

1. Jain BPet al. (2018) WD40 repeat proteins: signalling scaffold with diverse functions. Protein J37:391-406.