Structural Features of the Peptide Homologous to 6-25 Fragment of Influenza A PB1 Protein

A mirror-symmetry motif was discovered in the N-terminus of the influenza virus PB1 protein. Structure of peptide comprised of the corresponding part of PB1 (amino acid residues 6-25) was investigated by circular dichroism and in silico modeling. We found that peptide PB1 (6-25) in solution assumes beta-hairpin conformation. A truncated peptide PB1 (6-13), containing only half of the mirror-symmetry motif, appeared to stabilize the beta-structure of the original peptide and, at high concentrations, was capable of reacting with peptide to form insoluble aggregates in vitro. Ability of PB1 (6-13) peptide to interact with the N-terminal domain of PB1 protein makes it a potential antiviral agent that inhibits PA-PB1 complex formation by affecting PB1 N-terminus structure. 1. Introduction Peptides are a promising basis for the development of drugs. Creating peptide-based drugs includes the search of active sites or functionally important sites in the target protein and the selection of peptides capable of specific interaction with these sites. Such a selection usually can be accomplished using peptide libraries containing random fragments of amino acid sequences (irrational design) or fragments of natural proteins capable of reacting with target structural determinants. Developing approaches to rational design of potential peptide inhibitors of structural functional determinants of proteins can potentially expand the range of therapeutic medications based on peptides [1]. The key role in the process of development of an infection caused by the influenza virus is played by RNA polymerase. RNA polymerase of the influenza virus consists of three subunits—PA, PB1, and PB2. Assembling of PA and PB1 subunits of a polymerase complex occurs in cytoplasm of infected cells. Heterodimer is transported into the nucleus, where, upon accession of the third subunit—PB2, a functional polymerase complex is formed. According to the data of several authors, the critical region of the interaction of proteins PA and PB1 is the N-terminal region of protein PB1 [2, 3]. A number of studies [4, 5] showed that the structural determinant of the PA-PB1 interaction during formation of a polymerase complex of the influenza virus is fragment 1-15 of PB1 protein. The X-ray structural analysis of the crystals of the complex of the fragment of PA protein and the peptides corresponding to N-terminus of PB1 was carried out, and it showed that this fragment forms a system of hydrogen bonds with the C-terminal domain of PA. It was also shown that the presence of the polypeptide, containing the