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Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures
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2014 (English)In: Journal of Physical Chemistry Letters, ISSN 1948-7185, E-ISSN 1948-7185, Vol. 5, no 18, 3254-3258 p.Article in journal (Refereed) Published
Abstract [en]

Formation of superstructures in protein aggregation processes has been indicated as a general pathway for several proteins, possibly playing a role in human pathologies. There is a severe lack of knowledge on the origin of such species in terms of both mechanisms of formation and structural features. We use equine lysozyme as a model protein, and by combining spectroscopic techniques and microscopy with X-ray fiber diffraction and ab initio modeling of Small Angle X-ray Scattering data, we isolate the partially unfolded state from which one of these superstructures (i.e., particulate) originates. We reveal the low-resolution structure of the unfolded state and its mechanism of formation, highlighting the physicochemical features and the possible pathway of formation of the particulate structure. Our findings provide a novel detailed knowledge of such a general and alternative aggregation pathway for proteins, this being crucial for a basic and broader understanding of the aggregation phenomena.

Place, publisher, year, edition, pages
2014. Vol. 5, no 18, 3254-3258 p.
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Medical and Health Sciences
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URN: urn:nbn:se:umu:diva-96633DOI: 10.1021/jz501614eISI: 000343067700016OAI: oai:DiVA.org:umu-96633DiVA: diva2:766440
Available from: 2014-11-27 Created: 2014-11-24 Last updated: 2017-12-05Bibliographically approved

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Morozova-Roche, Ludmilla
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Department of Medical Biochemistry and Biophysics
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