Atomic force microscopy of spherical intermediates on the pathway to fibril formation of influenza A virus nuclear export protein.

Autor: Koroleva ON; Faculty of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation., Kuzmina NV; Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, Russian Federation., Dubrovin EV; Faculty of Physics, Lomonosov Moscow State University, Moscow, Russian Federation.; National University of Science and Technology, MISIS, Moscow, Russian Federation., Drutsa VL; A.N.Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation.
Jazyk: angličtina
Zdroj: Microscopy research and technique [Microsc Res Tech] 2024 Jun; Vol. 87 (6), pp. 1131-1145. Date of Electronic Publication: 2024 Jan 25.
DOI: 10.1002/jemt.24499
Abstrakt: The nuclear export protein of the influenza A virus (NEP) is involved in many important processes of the virus life cycle. This makes it an attractive target for the treatment of a disease caused by a virus. Previously it has been shown, that recombinant variants of NEP are highly prone to aggregation in solution under various conditions with the formation of amyloid-like aggregates. In the present work, the amyloid nature of NEP aggregates was evidenced by Congo red binding assays. Atomic force microscopy has shown that NEP can form two types of spherical nanoparticles, which provide an alternative pathway for the formation of amyloid-like fibrils. Type I of these "fibrillogenic" spheres, formed under physiological conditions, represents the micelle-like particles with height 10-60 nm, which can generate worm-like flexible fibrils with the diameter 2.5-4.0 nm, length 20-500 nm and the Young's modulus ~73 MPa. Type II spherical aggregates with size of about 400-1000 nm, formed at elevated temperatures, includes fractions of drop-like and vesicle-like particles, generating more rigid amyloid-like fibrils with height of ~8 nm, and length of up to 2 μm. The hypothetical mechanism of fibril formation via nanospherical structures was suggested. RESEARCH HIGHLIGHTS: AFM has revealed two types of the influenza A virus nuclear export protein spherical aggregates. They provide an alternative pathway for the formation of amyloid-like fibrils. The mechanism of fibril formation via spherical structures is suggested.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: