Structural flexibility and disassembly kinetics of single ferritin molecules using optical nanotweezers

Yousefi, A. ORCID: 0009-0009-5446-4656, Zheng, Z. ORCID: 0000-0002-9676-2856, Zargarbashi, S. ORCID: 0000-0001-7163-4949, Assadipapari, M. ORCID: 0009-0005-0222-5646, Hickman, G.J. ORCID: 0000-0002-4632-9229, Parmenter, C.D.J., Bueno-Alejo, C.J., Sanderson, G. ORCID: 0009-0005-0477-4163, Craske, D. ORCID: 0000-0003-3564-4108, Xu, L. ORCID: 0000-0001-9071-4311, Perry, C.C. ORCID: 0000-0003-1517-468X, Rahmani, M. ORCID: 0000-0001-9268-4793 and Ying, C. ORCID: 0000-0002-7279-1388, 2024. Structural flexibility and disassembly kinetics of single ferritin molecules using optical nanotweezers. ACS Nano, 18 (24), pp. 15617-15626. ISSN 1936-0851

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Abstract

Ferritin, a spherical protein shell assembled from 24 subunits, functions as an efficient iron storage and release system through its channels. Understanding how various chemicals affect the structural behavior of ferritin is crucial for unravelling the origins of iron-related diseases in living organisms including humans. In particular, the influence of chemicals on ferritin’s dynamics and iron release is barely explored at the single-protein level. Here, by employing optical nanotweezers using double-nanohole (DNH) structures, we examined the effect of ascorbic acid (reducing reagent) and pH on individual ferritin’s conformational dynamics. The dynamics of ferritin increased as the concentration of ascorbic acid approached saturation. At pH 2.0, ferritin exhibited significant structural fluctuations and eventually underwent a stepwise disassembly into fragments. This work demonstrated the disassembly pathway and kinetics of a single ferritin molecule in solution. We identified four critical fragments during its disassembly pathway, which are 22-mer, 12-mer, tetramer, and dimer subunits. Moreover, we present single-molecule evidence of the cooperative disassembly of ferritin. Interrogating ferritin’s structural change in response to different chemicals holds importance for understanding their roles in iron metabolism, hence facilitating further development of medical treatments for its associated diseases.

Item Type:	Journal article
Publication Title:	ACS Nano
Creators:	Yousefi, A., Zheng, Z., Zargarbashi, S., Assadipapari, M., Hickman, G.J., Parmenter, C.D.J., Bueno-Alejo, C.J., Sanderson, G., Craske, D., Xu, L., Perry, C.C., Rahmani, M. and Ying, C.
Publisher:	American Chemical Society (ACS)
Date:	18 June 2024
Volume:	18
Number:	24
ISSN:	1936-0851
Identifiers:	Number Type 10.1021/acsnano.4c01221 DOI 1916748 Other
Rights:	This publication is licensed under CC-BY 4.0.
Divisions:	Schools > School of Science and Technology
Record created by:	Jeremy Silvester
Date Added:	19 Jul 2024 09:56
Last Modified:	19 Jul 2024 09:56
URI:	https://irep.ntu.ac.uk/id/eprint/51784

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