Proline-, Glutamic Acid-, Leucine-Rich Protein 1 (PELP1): Diversity, Structural Conservation, and Evolutionary...

Proline-, Glutamic acid-, Leucine-rich Protein 1 (PELP1) is a multifunctional nuclear protein essential for ribosome biogenesis and steroid receptor signaling. It contains two hallmark domains: the RIX1 (Ribosome Export 1) domain, which mediates rRNA processing, and the NUC (nucleolar) domain, associated with nucleolar function. While PELP1's biological roles are well-characterized in mammals, particularly Homo sapiens, its distribution, structural diversity, and evolutionary origin across the domain of life remain largely unexplored. This study addresses this gap by conducting a comprehensive data mining of PELP1 proteins across the NCBI, UniProt, and EukProt databases. A total of 646 PELP1 proteins were identified exclusively in eukaryotes, specifically within the Opisthokonta clade, comprising Fungi, Filasterea, and Metazoa, while no homologs were detected in Bacteria, Viruses, Plants, or Oomycota. Domain analysis revealed that PELP1 proteins contain one RIX1 domain and one or two NUC202 domains. Motif analysis identified LXXLL and PXXP motifs, indicative of receptor-mediated signaling capability, although leucine and proline residues were not universally conserved within these motifs. Amino acid composition analysis showed enrichment of proline, glutamic acid, and cysteine across most PELP1 proteins. Despite low overall sequence identity, structural modeling demonstrated strong conservation of the α-helical fold, with an average root-mean-square deviation (RMSD) of 1.9 Å across species. Evolutionary analysis suggests that ancestral PELP1 emerged before the divergence of opisthokonts, originating from an RIX1-domain-containing protein that subsequently acquired a NUC202 domain. Phylogenetic clustering and sequence identity patterns resolved three major evolutionary lineages corresponding to fungi, filastereans, and metazoans. Overall, these findings reveal that PELP1 proteins exhibit extensive sequence divergence while maintaining a conserved structural architecture, reflecting evolutionary adaptation that preserves functional integrity across opisthokonts.