The amyloidogenicity of the influenza virus PB1-derived peptide sheds light on its antiviral activity.

Autor: Zabrodskaya YA; Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia. Electronic address: zabryaka@yandex.ru., Lebedev DV; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia., Egorova MA; Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia., Shaldzhyan AA; Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia., Shvetsov AV; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia; Peter the Great SaintPetersburg State Polytechnic University, St. Petersburg, Russia., Kuklin AI; Joint Institute for Nuclear Research, Dubna, Russia; Moscow Institute of Physics and Technology (State University), Moscow, Russia., Vinogradova DS; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia; NanoTemper Technologies Rus, St. Petersburg, Russia., Klopov NV; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia., Matusevich OV; Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia., Cheremnykh TA; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia., Dattani R; European Synchrotron Radiation Facility, Grenoble, France., Egorov VV; Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Center 'Kurchatov Institute', Gatchina, Russia; Federal State Budgetary Scientific Institution 'Institute of Experimental Medicine', St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Biophysical chemistry [Biophys Chem] 2018 Mar; Vol. 234, pp. 16-23. Date of Electronic Publication: 2018 Jan 08.
DOI: 10.1016/j.bpc.2018.01.001
Abstrakt: The influenza virus polymerase complex is a promising target for new antiviral drug development. It is known that, within the influenza virus polymerase complex, the PB1 subunit region from the 1st to the 25th amino acid residues has to be is in an alpha-helical conformation for proper interaction with the PA subunit. We have previously shown that PB1(6-13) peptide at low concentrations is able to interact with the PB1 subunit N-terminal region in a peptide model which shows aggregate formation and antiviral activity in cell cultures. In this paper, it was shown that PB1(6-13) peptide is prone to form the amyloid-like fibrillar aggregates. The peptide homo-oligomerization kinetics were examined, and the affinity and characteristic interaction time of PB1(6-13) peptide monomers and the influenza virus polymerase complex PB1 subunit N-terminal region were evaluated by the SPR and TR-SAXS methods. Based on the data obtained, a hypothesis about the PB1(6-13) peptide mechanism of action was proposed: the peptide in its monomeric form is capable of altering the conformation of the PB1 subunit N-terminal region, causing a change from an alpha helix to a beta structure. This conformational change disrupts PB1 and PA subunit interaction and, by that mechanism, the peptide displays antiviral activity.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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