Accelerated Amyloid Aggregation Dynamics of Intrinsically Disordered Proteins in Heavy Water.

Autor:	Son MK; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Proteogenome Research, Korea University, Seoul 02841, Republic of Korea., Im D; Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea., Hyun DG; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Proteogenome Research, Korea University, Seoul 02841, Republic of Korea., Kim S; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Proteogenome Research, Korea University, Seoul 02841, Republic of Korea., Chun SY; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science (IBS), Seoul 02841, Republic of Korea., Choi JM; Department of Chemistry, Pusan National University, Busan 46241, Republic of Korea.; Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea., Choi TS; Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea., Cho M; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science (IBS), Seoul 02841, Republic of Korea., Kwak K; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science (IBS), Seoul 02841, Republic of Korea., Kim HI; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.; Center for Proteogenome Research, Korea University, Seoul 02841, Republic of Korea.
Jazyk:	angličtina
Zdroj:	The journal of physical chemistry letters [J Phys Chem Lett] 2024 Nov 28; Vol. 15 (47), pp. 11823-11829. Date of Electronic Publication: 2024 Nov 19.
DOI:	10.1021/acs.jpclett.4c02764
Abstrakt:	We explored the influence of D 2 O on the fibrillation kinetics and structural dynamics of amyloid intrinsically disordered proteins (IDPs), including α-synuclein, amyloid-β 1-42, and K18. Our findings revealed that fibrillation of IDPs was accelerated in D 2 O compared to that in H 2 O, exhibiting faster kinetics in contrast to the structured protein, insulin. Structural investigations using electrospray ionization ion mobility mass spectrometry and small-angle X-ray scattering combined with molecular dynamics simulations demonstrated that IDPs did not show significant structural changes that could influence accelerated fibrillation in D 2 O. Umbrella sampling of protein protofibrils verified that an increased level of hydrogen bonding of D 2 O and enhanced hydrophobic interactions stabilized β-sheet structured fibrils in D 2 O. These findings indicate that stabilizing β-sheet fibrils and a more hydrophobic microenvironment in D 2 O result in enhanced and faster fibrillation of IDPs. The study highlights the importance of considering D 2 O's differential impact on protein interactions when conducting structural and kinetic analyses, particularly for native peptides and proteins.
Databáze:	MEDLINE
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