The “tale” of poly(A) binding protein: The MLLE domain and PAM2-containing proteins

The cytoplasmic poly(A) binding protein 1 (PABPC1) is an essential eukaryotic translational initiation factor first described over 40 years ago. Most studies of PABPC1 have focused on its N-terminal RRM domains, which bind the mRNA 3′ poly(A) tail and 5′ translation complex eIF4F via eIF4G; however, the protein also contains a C-terminal MLLE domain that binds a peptide motif, termed PAM2, found in many proteins involved in translation regulation and mRNA metabolism. Studies over the past decade have revealed additional functions of PAM2-containing proteins (PACs) in neurodegenerative diseases, circadian rhythms, innate defense, and ubiquitin-mediated protein degradation. Here, we summarize functional and structural studies of the MLLE/PAM2 interaction and discuss the diverse roles of PACs.