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A monomer-trimer model supports intermittent glucagon fibril growth

We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length 60μm. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis....

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Detalles Bibliográficos
Autores principales: Košmrlj, Andrej, Cordsen, Pia, Kyrsting, Anders, Otzen, Daniel E., Oddershede, Lene B., Jensen, Mogens H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355668/
https://www.ncbi.nlm.nih.gov/pubmed/25758791
http://dx.doi.org/10.1038/srep09005
Descripción
Sumario:We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length 60μm. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis. The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations. To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.