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

Vladimir V Egorov,Alexey K Sirotkin,Oleg I Kiselev,Alexey N Skvortsov,Andrey V Vasin,Aram A Shaldzhyan,Yana A Zabrodskaya,Dmitry V Lebedev,Oleg V Matusevich,Vladimir V Zarubayev,Sergey B Landa,Yuri P Garmay

doi:10.1155/2013/370832

Abstract

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.

Highlights

Peptides are a promising basis for the development of drugs
It was assumed that peptide PB1 (1-25) inside the cell forms a structure close to the structure of the N-terminal region of PB1 in the structure of PA-PB1 complex, interacts with protein PA, and prevents the formation of a polymerase complex required for viral replication
This studies show that the structure of the Nterminal region of protein PB1 is critical for the polymerase complex assembly and replication of the influenza virus

Summary

Introduction

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. It was assumed that peptide PB1 (1-25) inside the cell forms a structure close to the structure of the N-terminal region of PB1 in the structure of PA-PB1 complex, interacts with protein PA, and prevents the formation of a polymerase complex required for viral replication This studies show that the structure of the Nterminal region of protein PB1 is critical for the polymerase complex assembly and replication of the influenza virus

Methods

Results

Conclusion