Primary Nucleation Kinetics of Short Fibril-Forming Amyloidogenic Peptides

The Journal of Physical Chemistry. B
Jurriaan A Luiken, Peter G Bolhuis

Abstract

The primary nucleation step in amyloid fibril formation can, depending on the nature of peptide sequence, occur in one step, straight from a dilute solution, or in multiple steps, via oligomers or disordered aggregates. The precise kinetic pathways of these processes are poorly understood. Employing forward flux sampling and a midresolution coarse-grained force field, we analyzed the reactive pathways from the solvated state to the fibril nucleus for a system of 12 amyloidogenic peptides. In line with previous work, increasing the overall side-chain hydrophobicity switches the fibrillization mechanism from one- to two-step nucleation. Overall, in this mechanism, peptides first form dimers and trimers, which then grow into a β-sheet. This sheet serves as a template for nucleation of additional β sheets until the fibril nucleus is fully formed. Our simulations indicate that the presence of the recently predicted polymerized phase in the nucleation pathway of intermediately hydrophobic peptides slows down the dynamics of fibril formation considerably, which may influence the time scale on which toxic early oligomers exist. The structure of the amyloid fibrils was found to be strongly dependent on the relative hydrophobic strength ...Continue Reading

References

Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·F ChitiC M Dobson
Apr 25, 2002·Annual Review of Physical Chemistry·Peter G BolhuisPhillip L Geissler
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alessandro Laio, Michele Parrinello
Apr 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Thomas ScheibelSusan L Lindquist
Apr 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jörg GsponerAmedeo Caflisch
Oct 2, 2003·Nature Biotechnology·Shuguang Zhang
Sep 21, 2004·Biophysical Journal·Giorgio FavrinSandipan Mohanty
Nov 20, 2004·The Journal of Chemical Physics·M CecchiniA Caflisch
Feb 9, 2005·Physical Review Letters·Rosalind J AllenPieter Rein Ten Wolde
Jun 10, 2005·Nature·Rebecca NelsonDavid Eisenberg
Oct 1, 2005·Nature Materials·Raffaele MezzengaMartin Michel
Jan 21, 2006·The Journal of Chemical Physics·Rosalind J AllenPieter Rein ten Wolde
Feb 18, 2006·Journal of Molecular Biology·M CecchiniA Caflisch
Mar 7, 2006·Protein and Peptide Letters·Christopher M Dobson
Jun 8, 2006·Annual Review of Biochemistry·Fabrizio Chiti, Christopher M Dobson
Sep 13, 2006·The Journal of Chemical Physics·Philipp MetznerEric Vanden-Eijnden
Dec 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Phuong H NguyenD Thirumalai
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Christian Haass, Dennis J Selkoe
Feb 9, 2007·Journal of Neurochemistry·Dominic M Walsh, Dennis J Selkoe
Sep 25, 2007·The Journal of Chemical Physics·Chantal ValerianiPieter Rein ten Wolde
Nov 6, 2007·The Journal of Chemical Physics·Ernesto E Borrero, Fernando A Escobedo
Dec 7, 2007·Journal of the American Chemical Society·Birgit StrodelDavid J Wales
Jun 4, 2008·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Nicolae-Viorel Buchete, Gerhard Hummer
Sep 2, 2008·Biochemistry·Yan LiangDavid G Lynn
Nov 15, 2008·PLoS Computational Biology·Stefan AuerMichele Vendruscolo
Dec 18, 2008·Nature Chemical Biology·Fabrizio Chiti, Christopher M Dobson
Dec 31, 2008·Physical Review Letters·Stefan AuerAmos Maritan
Jun 25, 2009·The Journal of Chemical Physics·Tristan Bereau, Markus Deserno
Jul 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Govardhan ReddyD Thirumalai
Aug 15, 2009·Journal of the American Chemical Society·Kevin J ChannonCait E MacPhee
Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Magdalena I IvanovaDavid Eisenberg
Mar 23, 2010·Biophysical Journal·Allam S ReddyJuan J de Pablo
Apr 20, 2010·Journal of the American Chemical Society·Yan LiangKeith M Berland
Jan 5, 2011·The Journal of Chemical Physics·Joshua T Berryman, Tanja Schilling
Apr 20, 2011·Physical Chemistry Chemical Physics : PCCP·Marieke Schor, Peter G Bolhuis
Nov 18, 2009·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Rosalind J AllenPieter Rein Ten Wolde
Aug 2, 2011·Nature Nanotechnology·Tuomas P J Knowles, Markus J Buehler
Sep 15, 2011·Neurobiology of Learning and Memory·Sergio T Ferreira, William L Klein
Dec 27, 2011·Trends in Microbiology·Luz P BlancoMatthew R Chapman
Jan 27, 2012·Journal of the American Chemical Society·Fahimeh BaftizadehAlessandro Laio
Jun 23, 2012·Journal of Molecular Biology·Stefan AuerDimo Kashchiev
Dec 5, 2012·The Journal of Chemical Physics·Raffaela CabrioluStefan Auer

❮ Previous
Next ❯

Citations

Mar 12, 2016·The Journal of Physical Chemistry. B·Martín Carballo-Pacheco, Birgit Strodel
Oct 25, 2016·The Journal of Physical Chemistry. B·Florent X SmitPeter G Bolhuis
Jun 27, 2017·Physical Chemistry Chemical Physics : PCCP·Emanuel K Peter, Joan-Emma Shea
Jul 14, 2017·Physical Chemistry Chemical Physics : PCCP·Nidhi Katyal, Shashank Deep
Sep 17, 2017·The Journal of Chemical Physics·Nguyen Ba HungTrinh X Hoang
Apr 25, 2018·Chemical Society Reviews·Pim W J M FrederixSiewert J Marrink
Feb 3, 2018·The Journal of Chemical Physics·Jason HaagaJ M Rickman
Feb 18, 2020·The Journal of Chemical Physics·Sarwar Hussain, Amir Haji-Akbari
Sep 30, 2020·Biomolecules·Beata Szała-Mendyk, Andrzej Molski
Feb 12, 2021·Biophysical Journal·Jaehoon YangSherwin J Singer
Jan 20, 2021·The Journal of Physical Chemistry. B·Gregory-Neal Gomes, Zachary A Levine
Jan 10, 2020·Current Opinion in Structural Biology·Govardhan ReddyBalaka Mondal
Jul 13, 2021·The Journal of Physical Chemistry. B·Beata Szała-Mendyk, Andrzej Molski
Jul 21, 2017·The Journal of Physical Chemistry. B·Ming-Chien HsiehMartha A Grover
May 19, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Frédéric Gobeaux, Frank Wien
Oct 4, 2018·Chemical Reviews·Corey J WilsonJennifer M Heemstra

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.