Molecular dynamics and circular dichroism studies of human and rat C-peptides

Mares-Guia, Thiago Rennó dos; Maigret, Bernard; Martins, N. F.; Maia, Ana Luiza Turchetti; Vilela, Luciano; Ramos, Carlos H.I.; Neto, Luiz Juliano; Juliano, María A.; Mares-Guia, Marcos; Santoro, Marcelo M.

doi:10.1016/j.jmgm.2006.03.002

Cited by 11 publications

(9 citation statements)

References 47 publications

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“…1B). Ca 2+ was also observed to have some effect on oligomer distribution, with the most significant effect being a decrease in medium-order oligomers (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). In conclusion, divalent ions were seen to affect C-peptide oligomer formation.…”

Section: C-peptide Forms Oligomersmentioning

confidence: 80%

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Structural features of proinsulin C‐peptide oligomeric and amyloid states

et al. 2010

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The formation and structure of proinsulin C-peptide oligomers has been investigated by PAGE, NMR spectroscopy and dynamic light scattering. The results obtained show that C-peptide forms oligomers of different sizes, and that their formation and size distribution is altered by salt and divalent metal ions, which indicates that the aggregation process is mediated by electrostatic interactions. It is further demonstrated that the size distribution of the C-peptide oligomers, in agreement with previous studies, is altered by insulin, which supports a physiologically relevant interaction between these two peptides. A small fraction of oligomers has previously been suggested to be in equilibrium with a dominant fraction of soluble monomers, and this pattern also is observed in the present study. The addition of modest amounts of sodium dodecyl sulphate at low pH increases the relative amount of oligomers, and this effect was used to investigate the details of both oligomer formation and structure by a combination of biophysical techniques. The structural properties of the SDS-induced oligomers, as obtained by thioflavin T fluorescence, CD spectroscopy and IR spectroscopy, demonstrate that soluble aggregates are predominantly in b-sheet conformation, and that the oligomerization process shows characteristic features of amyloid formation. The formation of large, insoluble, b-sheet amyloid-like structures will alter the equilibrium between monomeric C-peptide and oligomers. This leads to the conclusion that the oligomerization of C-peptide may be relevant also at low concentrations.

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Section: C-peptide Forms Oligomersmentioning

confidence: 80%

“…Similar to many peptides, however, it has a propensity to form a a-helical structure in the presence of trifluoroethanol [15]. In addition, molecular dynamics simulations propose turn-like motifs in the midregion and in the C-terminal region [16].…”

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confidence: 95%

Structural features of proinsulin C‐peptide oligomeric and amyloid states

et al. 2010

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“…Driven by the possibility to understand C-peptide bioactivities, investigations were launched into the structural features of C-peptide, both as a part of proinsulin and as a free peptide in solution. Computational studies suggested a flexible architecture, potentially with a turn motif around residues 15-20 [37]. Solution NMR then provided the first high-resolution structure, confirming that C-peptide lacks a well-defined fold but exhibits some helical propensity in the C-terminal pentapeptide (Fig.…”

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

confidence: 88%

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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“…Apart from mature insulin, whose three dimensional structure was determined by X‐ray crystallography, proinsulin and C‐peptide adopt unordered structures in solution, as NMR spectroscopy confirmed and, interestingly, free insulin (chains A and B) displays similar overall conformation to that of proinsulin . Although most researchers agree that the C‐peptide structure is unordered under physiological conditions, a few studies reveal that C‐peptide is not a random coil, but rather contains detectable ordered structure both when free or attached to insulin in proinsulin; the N‐terminal part ( 1‐ EAEDLQVGQVE −11 ) may adopt an α‐helical conformation at high concentrations of trifluoroethanol (TFE) and Molecular Dynamics simulations suggest turn‐like motifs in the middle part and the C‐terminal of C‐peptide …”

Section: Introductionmentioning

confidence: 99%

“…The C‐terminal region contains an interaction epitope for binding to a G‐protein coupled receptor, while the C‐terminal pentapeptide 27‐ EGSLQ −31 specifically, simulates the way the full‐length C‐peptide binds to a cell surface . The middle segment (residues 12 − 26) of proinsulin C‐peptide, with a high turn propensity, is considered to be flexible due to its sequence composition and it is suggested to mediate C‐peptide – membrane interactions at low pH …”

Section: Introductionmentioning

confidence: 99%

Unraveling the aggregation propensity of human insulin C‐peptide

et al. 2017

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Over the last 20 years, proinsulin C-peptide emerged as an important player in various biological events. Much time and effort has been spent in exploring all functional features of C-peptide and recording its implications in Diabetes mellitus. Only a few studies, though, have addressed C-peptide oligomerization and link this procedure with Diabetes. The aim of our work was to examine the aggregation propensity of C-peptide, utilizing Transmission Electron Microscopy, Congo Red staining, ATR-FTIR, and X-ray fiber diffraction at a 10 mg ml concentration. Our experimental work clearly shows that C-peptide self-assembles into amyloid-like fibrils and therefore, the aggregation propensity of C-peptide is a characteristic novel feature that should be related to physiological and also pathological conditions. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 108: 1-8, 2017.

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Molecular dynamics and circular dichroism studies of human and rat C-peptides

Cited by 11 publications

References 47 publications

Structural features of proinsulin C‐peptide oligomeric and amyloid states

Structural features of proinsulin C‐peptide oligomeric and amyloid states

Biological activity versus physiological function of proinsulin C-peptide

Unraveling the aggregation propensity of human insulin C‐peptide

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