Scaffolded multimers of hIAPP20–29 peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP20–29 peptide fragment

Christoffersen, Heidi F.; Andreasen, Maria; Zhang, Shuai; Nielsen, Erik H.; Christiansen, Gunna; Dong, Mingdong; Skrydstrup, Troels; Otzen, Daniel E.

doi:10.1016/j.bbapap.2015.08.005

Cited by 12 publications

(11 citation statements)

References 54 publications

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“…Previous studies reported that Aβ 25–35 was able to bind to hIAPP with nanomolar affinity and the sequence of Aβ 25–35 was highly similar to the hIAPP 20–29 sequence 33 . Notably, hIAPP 20–29 was considered as the core region to modulate the self‐aggregation of hIAPP and might also be involved in hetero‐association pathways with other peptides 33,46 . It could be infered that the high sequence similarity of Aβ 25–35 and hIAPP 20–29 might improve their affinity of hIAPP and Aβ 25–35 .…”

Section: Resultsmentioning

confidence: 99%

“…33 Notably, hIAPP 20-29 was considered as the core region to modulate the self-aggregation of hIAPP and might also be involved in hetero-association pathways with other peptides. 33,46 It could be infered that the high sequence similarity of be observed directly, which implied that there was a tendency of conformations to more extend, the small difference in drift time (0.33 ms) could not be reflected in the calculation of CCS.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

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Studies on the cross‐interaction between hIAPP and Aβ_25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

et al. 2020

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A wealth of epidemiological evidence indicates a strong link between type 2 diabetes (T2D) and Alzheimer's disease (AD). The fiber deposition with cross-β-sheet structure formed by self-aggregation and misfolding of amyloidogenic peptides is a common hallmark of both diseases. For the patients with T2D, the fibrils are mainly found in the islets of Langerhans that results from the accumulation of human islet amyloid polypeptide (hIAPP). The major component of aggregates located in the brain of AD patients is amyloid-β (Aβ). Many biophysical and physiological properties are shared by hIAPP and Aβ, and both peptides show similar cytotoxic mechanisms. Therefore, it is meaningful to investigate the possible cross-interactions of hIAPP and Aβ in both diseases. In this article, the segment 25-35 of Aβ was selected because Aβ 25-35 was a core region in the process of amyloid formation and showed similar aggregation tendency and toxicity with full-length Aβ. The electrospray ionization-ion mobilitymass spectrometry analysis and thioflavin T fluorescence kinetic analysis combined with transmission electron microscopy were used to explore the effects of the coexistence of Aβ 25-35 and hIAPP on the self-aggregation of both peptides and whether there was co-assembly in fibrillation. The results indicated that the aggregation of hIAPP and Aβ 25-35 had two nucleation stages in the binary mixtures. hIAPP and Aβ 25-35 had a high binding affinity and a series of hetero-oligomers formed in the mixtures of hIAPP and Aβ 25-35 in the early stage. The cross-reaction between hIAPP monomers and Aβ 25-35 monomers as well as a little of oligomers during primary nucleation stage could accelerate the aggregation of Aβ 25-35. However, owing to the obvious difference in aggregation ability between hIAPP and Aβ 25-35 , this crossinteraction had no significant impact on the self-assembly of hIAPP. Our study may offer a better understanding for exploring the molecular mechanism of the association between AD and T2D observed in clinical and epidemiological studies and developing therapeutic strategies against amyloid diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Transmission Electron Microscopymentioning

confidence: 99%

Studies on the cross‐interaction between hIAPP and Aβ_25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

et al. 2020

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“…Growth rate, orientation, and deformation of the aggregation were greatly influenced by the substrates used in the experiments. Some correlations exist between substrates and amyloid fibrils conformation [4,11,16,29,30,42,99,107,108,135,148,149]. More and more results attributed this phenomenon to intermolecular interaction of static electronic interaction between amyloids and substrates [130,135,137,150,151].…”

Section: Substrate Effect Afm-based Experiments Indicatedmentioning

confidence: 96%

“…Improper aggregation of polypeptide fragments may result in various neurological disorder diseases [1], such as Alzheimer's disease (A aggregation) [2][3][4][5], Parkinson's disease [6], Huntington's disease (Huntington aggregation) [7,8], prion disease (PrP aggregation) [9], and amyotrophic lateral sclerosis (ALS) [10]. Amyloid aggregations are also found in type II diabetes (islet amyloid polypeptide) [11][12][13][14] and dialysis related amyloidosis ( -2 microglobulin aggregation) [6]. Recently, more and more studies have suggested that these diseases are related to the aggregations formed by amyloids sharing specific structural traits.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Inter- and Intramolecular Interactions of Amyloid Fibrils by AFM-Based Single-Molecule Force Spectroscopy

Liang

Zhao

et al. 2016

Journal of Nanomaterials

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Amyloids are fibrous protein aggregates defined by shared specific structural features. Abnormal accumulation of amyloid in organs leads to amyloidosis, which results in various neurodegenerative diseases. Atomic force microscopy (AFM) has proven to be an excellent tool investigating amyloids; it has been extensively utilized to characterize its morphology, assembly process, and mechanical properties. This review summarizes studies which applied AFM to detect the inter- and intramolecular interactions of amyloid fibrils and classified the influencing factors of amyloid’s nanomechanics in detail. The characteristics of amyloid fibrils driven by inter- and intramolecular interactions, including various morphologies of amyloid fibrils, self-assembly process, and the aggregating pathway, are described. Successful examples where AFM provided abundant information about inter- and intramolecular interactions of amyloid fibrils in different environments are presented. Direct force measurement of intra- or intermolecular interactions utilizing an AFM-based tool, single-molecular force spectroscopy (SMFS), is introduced. Some mechanical information such as elasticity, adhesiveness, and strength was obtained by stretching amyloid fibrils. This review helps researchers in understanding the mechanism of amyloidogenesis and exploring the properties of amyloid using AFM techniques.

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“…The short peptides, such as hIAPP 20-29 and hIAPP 18-27 , have been used in previous studies of amyloid aggregation and membrane disruption. [54][55][56][57][58][59] A variety of binding modes of hIAPP-Zn(II) and hIAPP-Cu(II) have been proposed based on the studies of hIAPP fragments, e.g., Ac-IAPP (15)(16)(17)(18)(19)(20)(21)(22)-NH 2 , Ac-IAPP (18)(19)(20)(21)(22)-NH 2 and its mutants, 60 Ac-PEG-IAPP(14-22)-NH 2 (ref. 20) and hIAPP(1-19).…”

Section: Introductionmentioning

confidence: 99%

Regulation of divalent metal ions to the aggregation and membrane damage of human islet amyloid polypeptide oligomers

Wang

Meng

et al. 2021

RSC Adv.

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Scaffolded multimers of hIAPP20–29 peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP20–29 peptide fragment

Cited by 12 publications

References 54 publications

Studies on the cross‐interaction between hIAPP and Aβ_25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

Studies on the cross‐interaction between hIAPP and Aβ_25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

Characterization of Inter- and Intramolecular Interactions of Amyloid Fibrils by AFM-Based Single-Molecule Force Spectroscopy

Regulation of divalent metal ions to the aggregation and membrane damage of human islet amyloid polypeptide oligomers

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Scaffolded multimers of hIAPP20–29 peptide fragments fibrillate faster and lead to different fibrils compared to the free hIAPP20–29 peptide fragment

Cited by 12 publications

References 54 publications

Studies on the cross‐interaction between hIAPP and Aβ25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

Studies on the cross‐interaction between hIAPP and Aβ25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

Characterization of Inter- and Intramolecular Interactions of Amyloid Fibrils by AFM-Based Single-Molecule Force Spectroscopy

Regulation of divalent metal ions to the aggregation and membrane damage of human islet amyloid polypeptide oligomers

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Product

Resources

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Studies on the cross‐interaction between hIAPP and Aβ_25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry

Studies on the cross‐interaction between hIAPP and Aβ_25–35 and the aggregation process in binary mixture by electrospray ionization‐ion mobility‐mass spectrometry