TITLE:
Comparative Structural and Functional Analysis of Viral Protein E3L and Human PKR dsRBM
AUTHORS:
Kai Chen, Zechang Rao, Xiaoju Zhong, Hongbin Zhang, Zihao Chen, Yousheng Hu
KEYWORDS:
PKR, E3L, Structural Comparison, Functional Analysis, Molecular Structure
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.3,
March
5,
2026
ABSTRACT: Objective: This study undertakes a bioinformatics analysis to compare the structures of the double-stranded RNA-binding motif (dsRBM) of the host protein kinase R (PKR) with that of the viral protein E3L from various poxviruses. The objective is to establish a foundational understanding of PKR’s antiviral mechanism and to inform drug design strategies. Methods involved selecting and retrieving E3L and PKR sequences from genome databases, followed by an analysis of their evolutionary relationships through sequence alignment and phylogenetic tree construction. The dsRBM structures of E3L and PKR were examined in both humans and zebrafish to investigate their molecular mechanisms and evolutionary systematics. Results from the sequence alignment of the dsRBMs of PKR and E3L in humans and zebrafish revealed that the aligned sequences were 67 amino acid sequences in length. Notably, the viral E3L and the third dsRBM of zebrafish PKR exhibited high conservation, with numerous conserved residues. It is hypothesized that E3L may be involved in the heterodimerization of the third dsRBM of zebrafish PKR, with the conserved amino acids critical for heterodimerization primarily located at positions 3, 5, 7, 8, 35, 37, 50, 51, 53, 56, 57, 58, 60, and 64. Phylogenetic tree analysis further suggested an evolutionary relationship between PKR and the viral protein E3L. It was also found through molecular docking software and scoring algorithms that its molecular structure has a high degree of similarity. Conclusion: The molecular spatial models of the dsRBM of viral protein E3L and human PKR both exhibit an α-β-β-β-α folding state. Despite the significant differences in their amino acid sequences, the molecular structures of viral protein E3L and PKR are highly similar. Based on this, it can be speculated that the two have a highly similar evolutionary origin.