Ferritin-based fusion protein shows octameric deadlock state of self-assembly.

Autor: Sudarev VV; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation., Gette MS; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation., Bazhenov SV; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation., Tilinova OM; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation., Zinovev EV; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation., Manukhov IV; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation., Kuklin AI; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, 141980, Russian Federation., Ryzhykau YL; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, 141980, Russian Federation. Electronic address: rizhikov@phystech.edu., Vlasov AV; Research Center for Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russian Federation; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, 141980, Russian Federation. Electronic address: aleksei.vlasov@phystech.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Jan 01; Vol. 690, pp. 149276. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1016/j.bbrc.2023.149276
Abstrakt: Ferritin is a universal protein complex responsible for iron perception in almost all living organisms and has applications from fundamental biophysics to drug delivery and structure-based immunogen design. Different platforms based on ferritin share similar technological challenges limiting their development - control of self-assembling processes of ferritin itself as well as ferritin-based chimeric recombinant protein complexes. In our research, we studied self-assembly processes of ferritin-based protein complexes under different expression conditions. We fused a ferritin subunit with a SMT3 protein tag, a homolog of human Small Ubiquitin-like Modifier (SUMO-tag), which was taken to destabilize ferritin 3-fold channel contacts and increase ferritin-SUMO subunits solubility. We first obtained the octameric protein complex of ferritin-SUMO (8xFer-SUMO) and studied its structural organization by small-angle X-ray scattering (SAXS). Obtained SAXS data correspond well with the high-resolution models predicted by AlphaFold and CORAL software of an octameric assembly around the 4-fold channel of ferritin without formation of 3-fold channels. Interestingly, three copies of 8xFer-SUMO do not assemble into 24-meric globules. Thus, we first obtained and structurally characterized ferritin-based self-assembling oligomers in a deadlock state. Deadlock oligomeric states of ferritin extend the known scheme of its self-assembly process, being new potential tools for a number of applications. Finally, our results might open new directions for various biotechnological platforms utilizing ferritin-based tools.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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