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dc.contributor.authorZaguri, Dor
dc.contributor.authorZimmermann, Manuela
dc.contributor.authorMeisl, Georg
dc.contributor.authorLevin, Aviad
dc.contributor.authorRencus-Lazar, Sigal
dc.contributor.authorKnowles, Tuomas
dc.contributor.authorGazit, Ehud
dc.date.accessioned2021-11-04T00:30:51Z
dc.date.available2021-11-04T00:30:51Z
dc.date.issued2021-10-25
dc.identifier.issn1936-0851
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330265
dc.description.abstractThe formation of ordered protein and peptide assemblies is a phenomenon related to a wide range of human diseases. However, the mechanism of assembly at the molecular level remains largely unknown. Minimal models enable the exploration of the underlying interactions that are at the core of such self-assembly processes. In particular, the ability of phenylalanine, a single aromatic amino acid, to form an amyloid-like structure has challenged the previous dogma viewing a peptide backbone as a prerequisite for assembly. The driving forces controlling the nucleation and assembly in the absence of a peptide backbone remain to be identified. Here, aiming to unravel these forces, we explored the kinetics and thermodynamics of three phenylalanine-containing molecules during their assembly process: the amino acid phenylalanine, which accumulates in phenylketonuria patients, the diphenylalanine core-motif of the amyloid β peptide related to Alzheimer's disease, and the extended triphenylalanine peptide which forms a range of distinct nanostructures in vitro. We found that the aggregation propensity, regarding the critical monomer concentration, strongly increases with size, with triphenylalanine being the most aggregation-prone species under our experimental conditions. In the context of classical nucleation theory, this increase in aggregation propensity can be attributed to the larger free energy decrease upon aggregation of larger peptides and is not due to the presence/absence of a peptide bond per se. Taken together, this work provides insights into the aggregation processes of chemically simple systems and suggests that both backbone-containing peptides and backbone-lacking amino acids assemble through a similar mechanism, thus supporting the classification of amino acids in the continuum of amyloid-forming building blocks.
dc.languageeng
dc.publisherAmerican Chemical Society
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectaggregation
dc.subjectnucleation
dc.subjectphenylalanine
dc.subjectself-assembly
dc.subjectthermodynamics
dc.subjectturbidity
dc.titleKinetic and Thermodynamic Driving Factors in the Assembly of Phenylalanine-Based Modules.
dc.typeArticle
prism.publicationNameACS Nano
dc.identifier.doi10.17863/CAM.77706
dcterms.dateAccepted2021-10-19
rioxxterms.versionofrecord10.1021/acsnano.1c07537
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-10-19
dc.contributor.orcidZimmermann, Manuela [0000-0002-3443-2050]
dc.contributor.orcidMeisl, Georg [0000-0002-6562-7715]
dc.contributor.orcidLevin, Aviad [0000-0002-3949-1033]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.identifier.eissn1936-086X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Research Council (337969)
cam.issuedOnline2021-10-25
cam.orpheus.success2021-11-03 - Embargo set during processing via Fast-track
rioxxterms.freetoread.startdate2022-10-25


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