Gesellschaft Deutscher Chemiker
Keine Benachrichtigungen
Sie haben noch keine Lesezeichen


Fibrils Emerging from Droplets: Molecular Guiding Principles behind Phase Transitions of a Short Peptide‐Based Condensate Studied by Solid‐State NMR

Von Wiley-VCH zur Verfügung gestellt

Phase transitions of short peptide-based condensates are studied by TEM and solid-state NMR spectroscopy. Structural modelling based on NMR distance restraints suggests that matured droplets are stabilized by hydrogen bonds along the fibril axis and side-chain π-π interactions, pointing to the possible role of such noncovalent interactions in liquid-to-solid transitions.


Biochemical reactions occurring in highly crowded cellular environments require different means of control to ensure productivity and specificity. Compartmentalization of reagents by liquid-liquid phase separation is one of these means. However, extremely high local protein concentrations of up to 400 mg/ml can result in pathological aggregation into fibrillar amyloid structures, a phenomenon that has been linked to various neurodegenerative diseases. Despite its relevance, the process of liquid-to-solid transition inside condensates is still not well understood at the molecular level. We thus herein use small peptide derivatives that can undergo both liquid-liquid and subsequent liquid-to-solid phase transition as model systems to study both processes. Using solid-state nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM), we compare the structure of condensed states of leucine, tryptophan and phenylalanine containing derivatives, distinguishing between liquid-like condensates, amorphous aggregates and fibrils, respectively. A structural model for the fibrils formed by the phenylalanine derivative was obtained by an NMR-based structure calculation. The fibrils are stabilised by hydrogen bonds and side-chain π-π interactions, which are likely much less pronounced or absent in the liquid and amorphous state. Such noncovalent interactions are equally important for the liquid-to-solid transition of proteins, particularly those related to neurodegenerative diseases.

Zum Volltext

Überprüfung Ihres Anmeldestatus ...

Wenn Sie ein registrierter Benutzer sind, zeigen wir in Kürze den vollständigen Artikel.