ArticleThe Journal of biological chemistry2014
Elucidating the role of disulfide bond on amyloid formation and fibril reversibility of somatostatin-14: relevance to its storage and secretion.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 76 citations in OpenAlex.
- The B22 Dilemma: Structural Basis for Conformational Differences in Proinsulin B-Chain Arg22 Mutants.Biomolecules · 2025Article
- Protein aggregates and biomolecular condensates: implications for human health and disease.Frontiers in molecular biosciences · 2025Review
- Amyloid formation and depolymerization of tumor suppressor p16Nature communications · 2024Article
- Nanoparticle-Based Secretory Granules Induce a Specific and Long-Lasting Immune Response through Prolonged Antigen Release.Nanomaterials (Basel, Switzerland) · 2024Article
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- Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Somatostatin slows Aβ plaque deposition in aged APPScientific reports · 2023Article
- Conformational and functional changes of the native neuropeptide somatostatin occur in the presence of copper and amyloid-β.Nature chemistry · 2022Article
- Structural insights into ligand recognition and selectivity of somatostatin receptors.Cell research · 2022Article
- Small disulfide loops in peptide hormones mediate self-aggregation and secretory granule sorting.Life science alliance · 2022Article
- Co-aggregation and secondary nucleation in the life cycle of human prolactin/galanin functional amyloids.eLife · 2022Article
- Aggregation of Aβ40/42 chains in the presence of cyclic neuropeptides investigated by molecular dynamics simulations.PLoS computational biology · 2021Article
- Fibrillation of Human Calcitonin and Its Analogs: Effects of Phosphorylation and Disulfide Reduction.Biophysical journal · 2021Article
- Enhanced neprilysin-mediated degradation of hippocampal Aβ42 with a somatostatin peptide that enters the brain.Theranostics · 2021Article
- Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins.International journal of molecular sciences · 2020Review
- Metal ions and redox balance regulate distinct amyloid-like aggregation pathways of GAPR-1.Scientific reports · 2019Article
- The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity.Molecules (Basel, Switzerland) · 2019Article
- Structural Analysis of Biomolecules through a Combination of Mobility Capillary Electrophoresis and Mass Spectrometry.ACS omega · 2019Article
- Article
- Oxetane Grafts Installed Site-Selectively on Native Disulfides to Enhance Protein Stability and Activity In Vivo.Angewandte Chemie (International ed. in English) · 2017Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The storage of protein/peptide hormones within subcellular compartments and subsequent release are crucial for their native function, and hence these processes are intricately regulated in mammalian systems. Several peptide hormones were recently suggested to be stored as amyloids within endocrine secretory granules. This leads to an apparent paradox where storage requires formation of aggregates, and their function requires a supply of non-aggregated peptides on demand. The precise mechanism behind amyloid formation by these hormones and their subsequent release remain an open question. To address this, we examined aggregation and fibril reversibility of a cyclic peptide hormone somatostatin (SST)-14 using various techniques. After proving that SST gets stored as amyloid in vivo, we investigated the role of native structure in modulating its conformational dynamics and self-association by disrupting the disulfide bridge (Cys(3)-Cys(14)) in SST. Using two-dimensional NMR, we resolved the initial structure of somatostatin-14 leading to aggregation and further probed its conformational dynamics in silico. The perturbation in native structure (S-S cleavage) led to a significant increase in conformational flexibility and resulted in rapid amyloid formation. The fibrils formed by disulfide-reduced noncyclic SST possess greater resistance to denaturing conditions with decreased monomer releasing potency. MD simulations reveal marked differences in the intermolecular interactions in SST and noncyclic SST providing plausible explanation for differential aggregation and fibril reversibility observed experimentally in these structural variants. Our findings thus emphasize that subtle changes in the native structure of peptide hormone(s) could alter its conformational dynamics and amyloid formation, which might have significant implications on their reversible storage and secretion.
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