Substrate recognition by TRIM and TRIM-like proteins in innate immunity

TRIM (Tripartite motif) and TRIM-like proteins have emerged as an important class of E3 ligases in innate immunity. Their functions range from activation or regulation of innate immune signaling pathway to direct detection and restriction of pathogens. Despite the importance, molecular mechanisms for many TRIM/TRIM-like proteins remain poorly characterized, in part due to challenges of identifying their substrates. In this review, we discuss several TRIM/TRIM-like proteins in RNA sensing pathways and viral restriction functions. We focus on those containing PRY-SPRY, the domain most frequently used for substrate recognition, and discuss emerging mechanisms that are commonly utilized by several TRIM/TRIM-like proteins to tightly control their interaction with the substrates.

Automated summary

TRIM/TRIM-like proteins play important roles in innate immunity, ranging from activation of immune signaling pathways to pathogen restriction. The molecular mechanisms of many TRIM/TRIM-like proteins are poorly understood due to substrate identification challenges. This review focuses on several TRIM/TRIM-like proteins in RNA sensing and viral restriction, emphasizing the PRY-SPRY domain for substrate recognition and shared control mechanisms for substrate interaction.