Structural Insights into Ankyrin Repeat-Containing Proteins and Their Influence in Ubiquitylation

Ankyrin repeat (AR) domains are considered the most abundant repeat motif found in eukaryotic proteins. AR domains are predominantly known to mediate specific protein-protein interactions (PPIs) without necessarily recognizing specific primary sequences, nor requiring strict conformity within its own primary sequence. This promiscuity allows for one AR domain to recognize and bind to a variety of intracellular substrates, suggesting that AR-containing proteins may be involved in a wide array of functions. Many AR-containing proteins serve a critical role in biological processes including the ubiquitylation signaling pathway (USP). There is also strong evidence that AR-containing protein malfunction are associated with several neurological diseases and disorders. In this review, the structure and mechanism of key AR-containing proteins are discussed to suggest and/or identify how each protein utilizes their AR domains to support ubiquitylation and the cascading pathways that follow upon substrate modification.

Automated summary

Ankyrin repeat (AR) domains are the most common repetitive structure in eukaryotic proteins, mediating specific protein-protein interactions and recognizing a variety of intracellular substrates. Proteins with AR domains play crucial roles in biological processes and their dysfunction is linked to neurological diseases and disorders. Understanding the structure and mechanism of key AR-containing proteins can provide insights into how they support ubiquitylation and subsequent signaling pathways.