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Physical determinan...
Physical determinants of the self-replication of protein fibrils
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- Šaric, Andela (författare)
- University of Cambridge,University College London
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- Buell, Alexander K. (författare)
- Heinrich Heine University Düsseldorf
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- Meisl, Georg (författare)
- University of Cambridge
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- Michaels, Thomas C T (författare)
- University of Cambridge
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- Dobson, Christopher M. (författare)
- University of Cambridge
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- Linse, Sara (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Knowles, Tuomas P J (författare)
- University of Cambridge
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- Frenkel, Daan (författare)
- University of Cambridge
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visa färre...
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(creator_code:org_t)
- 2016-07-18
- 2016
- Engelska 7 s.
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 12:9, s. 874-880
- Relaterad länk:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The ability of biological molecules to replicate themselves is the foundation of life, requiring a complex cellular machinery. However, a range of aberrant processes involve the self-replication of pathological protein structures without any additional assistance. One example is the autocatalytic generation of pathological protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders. Here, we use computer simulations to identify the necessary requirements for the self-replication of fibrillar assemblies of proteins. We establish that a key physical determinant for this process is the affinity of proteins for the surfaces of fibrils. We find that self-replication can take place only in a very narrow regime of inter-protein interactions, implying a high level of sensitivity to system parameters and experimental conditions. We then compare our theoretical predictions with kinetic and biosensor measurements of fibrils formed from the Aβ peptide associated with Alzheimer's disease. Our results show a quantitative connection between the kinetics of self-replication and the surface coverage of fibrils by monomeric proteins. These findings reveal the fundamental physical requirements for the formation of supra-molecular structures able to replicate themselves, and shed light on mechanisms in play in the proliferation of protein aggregates in nature.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
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- art (ämneskategori)
- ref (ämneskategori)
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