Unraveling the aggregation propensity of human insulin C‐peptide

Tsiolaki, Paraskevi L.; Louros, Nikolaos; Zompra, Aikaterini A.; Hamodrakas, Stavros J.; Iconomidou, Vassiliki A.

doi:10.1002/bip.22882

Cited by 3 publications

(3 citation statements)

References 83 publications

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“…It is worth mentioning that C-peptide has been reported to produce amyloid-like fibrils [36] .⁠ However, the timescale required experimentally for this peptide to develop a fully ordered structure ranges from minutes to days [36] , [47] .⁠ Our results are not contradictory with this biophysical evidence, as our simulations can capture only the early phases of aggregation. Indeed, this goes in line with the long-term effect of maturation and optimization of inter-glutamine interactions observed here.…”

Section: Discussionmentioning

confidence: 54%

Dissecting the role of glutamine in seeding peptide aggregation

Barrera

Zonta

Pantano

2021

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 54%

Dissecting the role of glutamine in seeding peptide aggregation

Barrera

Zonta

Pantano

2021

Computational and Structural Biotechnology Journal

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“…NMR studies showed that low pH shifted the conformational landscape of C-peptide towards a higher β-strand content. Electron microscopy, X-ray diffraction and FT-IR eventually confirmed that C-peptide, despite being highly soluble at physiological pH, spontaneously can form amyloid-like fibrils under acidic conditions [41,42].…”

Section: Phase 3: Combined Knowledge Of Structure Function and Evolumentioning

confidence: 87%

Biological activity versus physiological function of proinsulin C-peptide

Landreh

Jörnvall

2020

Cell. Mol. Life Sci.

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Proinsulin C-peptide (C-peptide) has drawn much research attention. Even if the peptide has turned out not to be important in the treatment of diabetes, every phase of C-peptide research has changed our view on insulin and peptide hormone biology. The first phase revealed that peptide hormones can be subject to processing, and that their pro-forms may involve regulatory stages. The second phase revealed the possibility that one prohormone could harbor more than one activity, and that the additional activities should be taken into account in the development of hormone-based therapies. In the third phase, a combined view of the evolutionary patterns in hormone biology allowed an assessment of C-peptide´s role in physiology, and of how biological activities and physiological functions are shaped by evolutionary processes. In addition to this distinction, C-peptide research has produced further advances. For example, C-peptide fragments are successfully administered in immunotherapy of type I diabetes, and plasma C-peptide levels remain a standard for measurement of beta cell activity in patients. Even if the concept of C-peptide as a hormone is presently not supported, some of its bioactivities continue to influence our understanding of evolutionary changes of also other peptides.

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“…The conventional 86-AA proinsulin is prefolded into its correct conformation in the Golgi apparatus, together with C-peptide ( 26 ). The N-terminus of the 31-AA C-peptide (EAEDLQVGQ) acts as a chaperone ( 27 ) to promote correct insulin folding, while its C-terminus (EGSLQ), in circulation, is known to bind the orphan G-protein–coupled receptor GPR146 ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Novel Human Insulin Isoforms and Cα-Peptide Product in Islets of Langerhans and Choroid Plexus

et al. 2021

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Plasma samples were assayed for insulin (Mercordia, Winston Salem, NC Cat# 10-1113-01) and C-peptide (Mercodia, Cat# 10-1136-01) by ELISA (1). Proteins were precipitated from postmortem frozen blood samples by orderly mixing 1 ml of ice-cold acetone, 0.125 ml trichloroacetic acid (6.1 N), and 0.125 ml of thawed frozen blood and vortex vigorously for 1.5 min. After -20 0 C overnight precipitation, the pellets were collected by centrifugation at 13,000 x g for 15 min at 4°C and washed 5 times by vigorous vortex and centrifugation at 8,000 x g for 5 min with 1 ml of acetone and air dry completely before dissolving in 0.5 ml phosphate-buffered saline (PBS) for C-peptide ELISA (2). SRM-MS analysis Brief:The method includes: 1) the selection of potential tryptic peptides based on the alternative splicing sites, i.e., pep-U1, -U2, and -U3 peptides are encoded by the exon-1U, and the pep-U4 and pep-U5 peptides are non-canonically encoded by intron-1, and pep-UF (frameshift) by intron-2 (Fig 1 and Fig 2A; Supplemental Table 4). Pep-US is encoded by spliced exon-1UB and exon-2 (Fig 2B and Supplemental Fig 1A-G). The pep-B (B-chain) is encoded by exon-2 and located after the signal peptide, while the pep-A (A-chain) is encoded by exon-3 (Supplemental

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Unraveling the aggregation propensity of human insulin C‐peptide

Cited by 3 publications

References 83 publications

Dissecting the role of glutamine in seeding peptide aggregation

Dissecting the role of glutamine in seeding peptide aggregation

Biological activity versus physiological function of proinsulin C-peptide

Novel Human Insulin Isoforms and Cα-Peptide Product in Islets of Langerhans and Choroid Plexus

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