TY - JOUR
T1 - Infrared Laser-Induced Amyloid Fibril Dissociation
T2 - A Joint Experimental/Theoretical Study on the GNNQQNY Peptide
AU - Kawasaki, Takayasu
AU - Man, Viet Hoang
AU - Sugimoto, Yasunobu
AU - Sugiyama, Nobuyuki
AU - Yamamoto, Hiroko
AU - Tsukiyama, Koichi
AU - Wang, Junmei
AU - Derreumaux, Philippe
AU - Nguyen, Phuong H.
N1 - Funding Information:
This work has been supported by the Department of Science and Technology at Ho Chi Minh City, Vietnam (Grant 13/2020/H-QPTKHCN), the Initiative d’Excellence program from the French State (Grant DYNAMO, ANR-11-LABX-0011-01, and CACSICE, ANR-11-EQPX-0008), and the National Institutes of Health (R01-GM079383, R21-GM097617, and P30-DA035778). We are grateful to Photon Beam Platform Project of the Ministry of Education, Culture, Sports, Science and Technology of Japan. The X-ray scattering experiment was conducted at Aichi Synchrotron Radiation Center, Aichi Science & Technology Foundation, Aichi, Japan (proposal no. 201703078). This work was partly supported by Private University Research Branding Project organized (MEXT) for Water Frontier Science & Technology Research Center of Tokyo University of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding organizations. Computational support from the IDRIS, CINES, TGCC centers (project A0080711440), and the Center for Research Computing of University of Pittsburgh, and the Extreme Science and Engineering Discovery Environment (CHE090098, MCB170099, and MCB180045P), are acknowledged.
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/7/23
Y1 - 2020/7/23
N2 - Neurodegenerative diseases are usually characterized by plaques made of well-ordered aggregates of distinct amyloid proteins. Dissociating these very stable amyloid plaques is a critical clinical issue. In this study, we present a joint mid-infrared free electron laser experiment/nonequilibrium molecular dynamics simulation to understand the dissociation process of a representative example GNNQQNY fibril. By tuning the laser frequency to the amide I band of the fibril, the resonance takes place and dissociation is occurred. With the calculated and observed wide-angle X-ray scattering profiles and secondary structures before and after laser irradiation being identical, we can propose a dissociation mechanism with high confidence from our simulations. We find that dissociation starts in the core of the fibrils by fragmenting the intermolecular hydrogen bonds and separating the peptides and then propagates to the fibril extremities leading to the formation of unstructured expanded oligomers. We suggest that this should be a generic mechanism of the laser-induced dissociation of amyloid fibrils.
AB - Neurodegenerative diseases are usually characterized by plaques made of well-ordered aggregates of distinct amyloid proteins. Dissociating these very stable amyloid plaques is a critical clinical issue. In this study, we present a joint mid-infrared free electron laser experiment/nonequilibrium molecular dynamics simulation to understand the dissociation process of a representative example GNNQQNY fibril. By tuning the laser frequency to the amide I band of the fibril, the resonance takes place and dissociation is occurred. With the calculated and observed wide-angle X-ray scattering profiles and secondary structures before and after laser irradiation being identical, we can propose a dissociation mechanism with high confidence from our simulations. We find that dissociation starts in the core of the fibrils by fragmenting the intermolecular hydrogen bonds and separating the peptides and then propagates to the fibril extremities leading to the formation of unstructured expanded oligomers. We suggest that this should be a generic mechanism of the laser-induced dissociation of amyloid fibrils.
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U2 - 10.1021/acs.jpcb.0c05385
DO - 10.1021/acs.jpcb.0c05385
M3 - Article
C2 - 32560588
AN - SCOPUS:85088489702
SN - 1520-6106
VL - 124
SP - 6266
EP - 6277
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 29
ER -