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Proton Transfer and Structure-Specific Fluorescence in Hydrogen Bond-Rich Protein Structures.

Accepted version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Pinotsi, Dorothea 
Grisanti, Luca 
Mahou, Pierre 
Gebauer, Ralph 
Kaminski, Clemens F 

Abstract

Protein structures which form fibrils have recently been shown to absorb light at energies in the near UV range and to exhibit a structure-specific fluorescence in the visible range even in the absence of aromatic amino acids. However, the molecular origin of this phenomenon has so far remained elusive. Here, we combine ab initio molecular dynamics simulations and fluorescence spectroscopy to demonstrate that these intrinsically fluorescent protein fibrils are permissive to proton transfer across hydrogen bonds which can lower electron excitation energies and thereby decrease the likelihood of energy dissipation associated with conventional hydrogen bonds. The importance of proton transfer on the intrinsic fluorescence observed in protein fibrils is signified by large reductions in the fluorescence intensity upon either fully protonating, or deprotonating, the fibrils at pH = 0 or 14, respectively. Thus, our results point to the existence of a structure-specific fluorophore that does not require the presence of aromatic residues or multiple bond conjugation that characterize conventional fluorescent systems. The phenomenon may have a wide range of implications in biological systems and in the design of self-assembled functional materials.

Description

Keywords

Amyloid, Amyloid beta-Peptides, Hydrogen Bonding, Microscopy, Atomic Force, Microscopy, Fluorescence, Molecular Dynamics Simulation, Peptide Fragments, Protein Structure, Secondary, Proteins, Protons, Spectrometry, Fluorescence, Structure-Activity Relationship

Journal Title

J Am Chem Soc

Conference Name

Journal ISSN

0002-7863
1520-5126

Volume Title

138

Publisher

American Chemical Society (ACS)
Sponsorship
Wellcome Trust (089703/Z/09/Z)
Medical Research Council (MR/K015850/1)
Engineering and Physical Sciences Research Council (EP/H018301/1)
Medical Research Council (MC_G1000734)
Medical Research Council (MR/K02292X/1)
Medical Research Council (MR/N012453/1)
We thank Prof. M. Sauer for useful discussions. This work was funded by grants from the Medical Research Council UK (MR/K015850/1 and MR/K02292X/1), Alzheimer Research UK (ARUKEG2012A-1), U.K. EPSRC (EP/H018301/1) and the Wellcome Trust (089703/Z/09/Z). D.P. wishes to acknowledge support from the Swiss National Science Foundation and the Wellcome Trust through personal fellowships. We thank LMB Visual Aids for graphics support.