Femtosecond X-ray coherent diffraction of aligned amyloid fibrils on low background graphene. Infectious and noninfectious amyloids of the HET-s(218-289) prion have different NMR spectra. Amyloid fibril polymorphism: almost identical on the atomic level, mesoscopically very different. Protocols for the sequential solid-state NMR spectroscopic assignment of a uniformly labeled 25 kDa protein: HET-s(1-227). Mast cell granule heparin proteoglycan induces lacunae in confluent endothelial cell monolayers. The pH of the secretory pathway: measurement, determinants, and regulation. Heparin acts as a structural component of β-endorphin amyloid fibrils rather than a simple aggregation promoter. Dynamic assembly and disassembly of functional β-endorphin amyloid fibrils. The peptide hormone glucagon forms amyloid fibrils with two coexisting β-strand conformations. Structural characterization of amyloid fibrils from the human parathyroid hormone. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Concentrating hormones into secretory granules: layers of control.
Sorting and storage during secretory granule biogenesis: looking backward and looking forward. Pathways of protein secretion in eukaryotes. Structure-activity relationship of amyloid fibrils. Amyloid aggregates of the HET-s prion protein are infectious. L., Dos Reis, S., Duvezin-Caubet, S., Coulary-Salin, B. Amyloids-a functional coat for microorganisms. G., Claessen, D., Bouma, B., Dijkhuizen, L. Functional amyloid formation within mammalian tissue.
Role of Escherichia coli curli operons in directing amyloid fiber formation. Analyses of β-endorphin variants carrying mutations in Glu8 support the role of the protonation state of this residue in fibril disassembly, among other environmental changes.Ĭhapman, M. The secretory granule has an acidic pH but, on exocytosis, the β-endorphin fibril would encounter neutral pH conditions (pH 7.4) in the blood this pH change would result in deprotonation of Glu8 to release the hormone peptide from the amyloid. In the β-endorphin amyloid, every layer of the β-solenoid is composed of a single peptide and protonated Glu8 is located in the fibrillar core. We find that β-endorphin fibrils are in a β-solenoid conformation that is generally reminiscent of other functional amyloids. Here, we use solid-state NMR to determine the 3D structure of the amyloid fiber formed by the human hormone β-endorphin. In the pituitary gland, peptide hormones can be stored as amyloid fibrils within acidic secretory granules before release into the blood stream. For amyloid disassembly in the blood, it is proposed that the pH change acts together with a buffer composition change and hormone dilution. During exocytosis of the hormone amyloid the pH increases from acidic in the secretory granule to neutral level in the blood, thus it is suggested-and supported with mutagenesis data-that the pH change in the cellular milieu acts through the deprotonation of glutamate 8 to release the hormone from the amyloid. We find that β-endorphin fibrils are in a β-solenoid conformation with a protonated glutamate residue in their fibrillar core. To gain a detailed understanding of the structure–function relationship of amyloids in hormone secretion, the three-dimensional (3D) structure of the amyloid fibril of the human hormone β-endorphin was determined by solid-state NMR. In the pituitary gland, hormones are stored in a functional amyloid state within acidic secretory granules before they are released into the blood.