WD40 repeat

WD40 repeat (also known as WD repeat or WD40 domain) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. WD40 domains are found in a multitude of eukaryotic proteins, serving as a versatile scaffold for protein-protein interactions. These repeats are responsible for assembling multiprotein complexes involved in a wide range of critical cellular functions including signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly, and the cell cycle.

Structure

The WD40 repeat forms a beta-propeller structure, with each WD40 domain acting as a blade in the propeller. Typically, a protein contains several WD repeats that fold together to form a circular, propeller-like structure with 6 to 8 blades. Each blade consists of a four-stranded anti-parallel beta-sheet. The propeller structure provides a stable platform for protein-protein interactions, with the top and bottom faces of the propeller serving as interaction sites.

Function

WD40 repeat-containing proteins are involved in a variety of cellular processes. The versatility of the WD40 domain in mediating protein-protein interactions lies in its ability to bind multiple partners and facilitate the assembly of protein complexes. This adaptability is crucial for the dynamic assembly and disassembly of cellular complexes in response to cellular signals.

Signal Transduction

In signal transduction pathways, WD40 repeat proteins act as scaffolds that organize the components of a signaling cascade, ensuring specificity and fidelity of the signal. For example, the G protein beta subunit, which contains a WD40 domain, plays a critical role in G protein-coupled receptor (GPCR) signaling pathways.

Cell Cycle Control

WD40 repeat proteins are also key players in the control of the cell cycle. They are involved in the regulation of cyclin-dependent kinases (CDKs), which are essential for cell cycle progression. The WD40 protein Cdc20 is a coactivator of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets cell cycle proteins for degradation, thereby regulating the cell cycle.

RNA Processing

In RNA processing, WD40 proteins participate in the assembly of the spliceosome, a complex responsible for the removal of introns from pre-mRNA. The WD40 domain-containing protein Prp19 is involved in the activation of the spliceosome.

Gene Regulation

WD40 repeat proteins play roles in chromatin remodeling and transcriptional regulation. For instance, WDR5, a WD40 protein, is a component of the SET1 family of histone methyltransferases, which are involved in the methylation of histone H3 and the regulation of gene expression.

Examples

Some well-known proteins containing WD40 repeats include:

• G protein beta subunit - involved in GPCR signaling
• Cdc20 - involved in cell cycle control
• Prp19 - involved in RNA splicing
• WDR5 - involved in histone modification and gene regulation

Clinical Significance

Mutations in WD40 repeat-containing proteins have been implicated in a variety of human diseases, including cancer, neurodegenerative diseases, and developmental disorders. The versatility of WD40 domains in protein-protein interactions makes them potential targets for therapeutic intervention.

See Also

• Protein domain
• Signal transduction
• Cell cycle
• RNA splicing
• Histone modification

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