Issue 99, 2016

Molecules of Congo red caught hopping between insulin fibrils: a chiroptical probe of the dye–amyloid binding dynamics

Abstract

Misfolded protein molecules tend to self-assemble into highly-ordered aggregates, the so-called amyloid fibrils whose presence in vivo is often symptomatic of certain neurodegenerative disorders. Amyloid fibrils from different proteins share the capacity to bind a number of small planar molecules such as Congo Red (CR). The underlying docking interactions between fibrils and ligands remain poorly understood despite their importance for research on amyloid-inhibiting drugs. Here, we describe a novel approach to study binding of small ligands to amyloid fibrils. We probe dynamics of CR–amyloid interactions using two structural variants of insulin fibrils with strong quasi-opposite chiroptical properties and the ability to induce circular dichroism in bound CR molecules. We demonstrate that in mixed non-equilibrium complexes of CR with both chiral variants of fibrils, dissociation of CR–amyloid complex is the rate-determining step of the overall equilibration of the system. Kinetics of entropy-driven “hopping” of CR molecules between saturated and unoccupied binding moieties on amyloid fibrils follow exponential trajectories enabling calculation of dissociation rates of CR–amyloid complex. Temperature dependencies of CR-exchange rates reveal a heterogeneous distribution of CR–amyloid binding energies in the range of 38–53 kJ mol−1. Our results have been discussed in the context of mechanisms of interactions between amyloid fibrils and amyloid-specific stains.

Graphical abstract: Molecules of Congo red caught hopping between insulin fibrils: a chiroptical probe of the dye–amyloid binding dynamics

Article information

Article type
Paper
Submitted
02 Sep 2016
Accepted
05 Oct 2016
First published
05 Oct 2016

RSC Adv., 2016,6, 97331-97337

Molecules of Congo red caught hopping between insulin fibrils: a chiroptical probe of the dye–amyloid binding dynamics

R. Dec, V. Babenko and W. Dzwolak, RSC Adv., 2016, 6, 97331 DOI: 10.1039/C6RA22067C

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