Sampling the self-assembly pathways of KFFE hexamers

Biophysical Journal
Guanghong WeiPhilippe Derreumaux

Abstract

The formation of amyloid fibrils is often encountered in Alzheimer's disease, type II diabetes, and transmissible spongiform encephalopathies. In the last few years, however, mounting evidence has suggested that the soluble oligomers of amyloid-forming peptides are also cytotoxic agents. Understanding the early pathway steps of amyloid self-assembly at atomic detail might therefore be crucial for the development of specific inhibitors to prevent amyloidosis in humans. Using the activation-relaxation technique and a generic energy model, we study in detail the aggregation of a hexamer of KFFE peptide. Our simulations show that a monomer remains disordered, but that six monomers placed randomly in an open box self-associate to adopt, with various orientations, three possible distant low-energy structures. Two of these structures show a double-layer beta-sheet organization, in agreement with the structure of amyloid fibrils as observed by x-ray diffraction, whereas the third one consists of a barrel-like curved single-layer hexamer. Based on these results, we propose a bidirectional growth mode of amyloid fibril, involving alternate lateral and longitudinal growths.

References

Jun 1, 1995·Proteins·R Srinivasan, G D Rose
Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich
Nov 18, 1996·Physical Review Letters·G T Barkema, N Mousseau
May 18, 1999·Biophysical Chemistry·J MaselM A Nowak
Mar 29, 2001·Protein Science : a Publication of the Protein Society·P M HarrisonF E Cohen
Dec 4, 2001·Biochimica Et Biophysica Acta·E T Jaikaran, A Clark
Apr 23, 2002·Protein Science : a Publication of the Protein Society·R I Dima, D Thirumalai
Jun 18, 2002·Science·J Paul TaylorKenneth H Fischbeck
Sep 7, 2002·The Journal of Biological Chemistry·Lars TjernbergJan Johansson
Nov 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Manuela López De La PazLuis Serrano
Apr 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jörg GsponerAmedeo Caflisch
Jun 28, 2003·Biophysical Journal·S Y FungP Chen
Aug 28, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Massimo Stefani, Christopher M Dobson
Nov 5, 2003·Biochemistry·Brett A ChromyWilliam L Klein
Jan 6, 2004·The Journal of Biological Chemistry·Janelle D GreenUeli Aebi
Jan 20, 2004·Journal of Molecular Biology·O Sumner Makin, Louise C Serpell
Jan 31, 2004·The Journal of Biological Chemistry·Brian O'NuallainRonald Wetzel
Jul 2, 2004·Proteins·Guanghong WeiPhilippe Derreumaux
Jul 10, 2004·Structure·Sébastien SantiniPhilippe Derreumaux

❮ Previous
Next ❯

Citations

Feb 10, 2009·Nano Letters·Idit BuchRuth Nussinov
Dec 6, 2008·PLoS Computational Biology·Da-Wei LiShuanghong Huo
Dec 5, 2012·PLoS Computational Biology·Jessica Nasica-Labouze, Normand Mousseau
Sep 26, 2009·The Journal of Chemical Physics·Giovanni Bellesia, Joan-Emma Shea
Feb 22, 2013·The Journal of Chemical Physics·Boris Ni, Andrij Baumketner
Jan 28, 2012·The Journal of Chemical Physics·L Dupuis, Normand Mousseau
Sep 13, 2006·The Journal of Chemical Physics·Wei ChenPhilippe Derreumaux
Apr 17, 2009·The Journal of Chemical Physics·Giovanni Bellesia, Joan-Emma Shea
Dec 3, 2008·The Journal of Chemical Physics·Mai Suan LiD Thirumalai
Feb 23, 2007·The Journal of Chemical Physics·Adrien MelquiondPhilippe Derreumaux
Feb 17, 2011·The Journal of Chemical Physics·Jason Gee, M Scott Shell
May 25, 2005·The Journal of Chemical Physics·Adrien MelquiondPhilippe Derreumaux
Aug 9, 2006·Proteins·Adrien MelquiondPhilippe Derreumaux
Nov 22, 2005·Proteins·Xiaoling WangRohit V Pappu
Oct 5, 2006·Proteins·Geneviève BoucherPhilippe Derreumaux
Feb 3, 2009·Biophysical Journal·Giovanni Bellesia, Joan-Emma Shea
Jun 27, 2006·Journal of Molecular Biology·Riccardo Pellarin, Amedeo Caflisch
Apr 17, 2015·The Journal of Chemical Physics·Maksim KouzaMai Suan Li
Nov 22, 2007·Journal of Molecular Biology·Riccardo PellarinAmedeo Caflisch
Oct 5, 2016·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Mara ChiricottoSimone Melchionna
Jan 1, 2007·Prion·Guanghong WeiPhilippe Derreumaux
Mar 25, 2019·The Journal of Chemical Physics·Ushnish SenguptaBirgit Strodel
Apr 1, 2008·Journal of Chemical Theory and Computation·Birgit Strodel, David J Wales
Jul 24, 2008·The Journal of Physical Chemistry. B·Birgit StrodelDavid J Wales
Aug 25, 2010·The Journal of Physical Chemistry. B·Edmund I Lin, M Scott Shell
Jan 27, 2012·Journal of the American Chemical Society·Fahimeh BaftizadehAlessandro Laio
Jan 31, 2012·The Journal of Physical Chemistry. B·Yassmine ChebaroPhilippe Derreumaux
Mar 20, 2015·Chemical Reviews·Jessica Nasica-LabouzePhilippe Derreumaux

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.