6533b7d6fe1ef96bd1266861
RESEARCH PRODUCT
Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures.
Thea S WindBente VestergaardLudmilla A. Morozova-rocheClaus CornettVito FoderàValeria VetriAthene M. DonaldWim Noppesubject
unfolded stateChemistryMechanism (biology)Ab initioModel proteinamyloid superstructure SAXS Spectroscopy Fluorescence microscopy dye diffusionNanotechnologyProtein aggregationBiophysicsGeneral Materials ScienceLack of knowledgePhysical and Theoretical Chemistryconformational changesFiber diffractionparticulateprotein superstructureshydrophobicitydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-09-09 |