Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy

Shuai Zhang; Maria Andreasen; Jakob T Nielsen; Lei Liu; Erik H Nielsen; Jie Song; Gang Ji; Fei Sun; Troels Skrydstrup; Flemming Besenbacher; Niels C Nielsen; Daniel E Otzen; Mingdong Dong

doi:10.1073/pnas.1209955110

Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy

Shuai Zhang, Maria Andreasen, Jakob T Nielsen, Lei Liu, Erik H Nielsen, Jie Song, Gang Ji, Fei Sun, Troels Skrydstrup, Flemming Besenbacher, Niels C Nielsen, Daniel E Otzen, Mingdong Dong

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

Uncontrolled misfolding of proteins leading to the formation of amyloid deposits is associated with more than 40 types of diseases, such as neurodegenerative diseases and type-2 diabetes. These irreversible amyloid fibrils typically assemble in distinct stages. Transitions among the various intermediate stages are the subject of many studies but are not yet fully elucidated. Here, we combine high-resolution atomic force microscopy and quantitative nanomechanical mapping to determine the self-assembled structures of the decapeptide hIAPP(20-29), which is considered to be the fibrillating core fragment of the human islet amyloid polypeptide (hIAPP) involved in type-2 diabetes. We successfully follow the evolution of hIAPP(20-29) nanostructures over time, calculate the average thickening speed of small ribbon-like structures, and provide evidence of the coexistence of ribbon and helical fibrils, highlighting a key step within the self-assembly model. In addition, the mutations of individual side chains of wide-type hIAPP(20-29) shift this balance and destabilize the helical fibrils sufficiently relative to the twisted ribbons to lead to their complete elimination. We combine atomic force microscopy structures, mechanical properties, and solid-state NMR structural information to build a molecular model containing β sheets in cross-β motifs as the basis of self-assembled amyloids.

Original language	English
Journal	Proceedings of the National Academy of Sciences (PNAS)
Volume	110
Issue	8
Pages (from-to)	2798-2803
Number of pages	6
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.1209955110
Publication status	Published - 2013

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10.1073/pnas.1209955110

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Zhang, S., Andreasen, M., Nielsen, J. T., Liu, L., Nielsen, E. H., Song, J., Ji, G., Sun, F., Skrydstrup, T., Besenbacher, F., Nielsen, N. C., Otzen, D. E., & Dong, M. (2013). Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy. Proceedings of the National Academy of Sciences (PNAS), 110(8), 2798-2803. https://doi.org/10.1073/pnas.1209955110

@article{1bf832f16e2f49a1b2c2a9e19ea734b0,

title = "Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy",

abstract = "Uncontrolled misfolding of proteins leading to the formation of amyloid deposits is associated with more than 40 types of diseases, such as neurodegenerative diseases and type-2 diabetes. These irreversible amyloid fibrils typically assemble in distinct stages. Transitions among the various intermediate stages are the subject of many studies but are not yet fully elucidated. Here, we combine high-resolution atomic force microscopy and quantitative nanomechanical mapping to determine the self-assembled structures of the decapeptide hIAPP(20-29), which is considered to be the fibrillating core fragment of the human islet amyloid polypeptide (hIAPP) involved in type-2 diabetes. We successfully follow the evolution of hIAPP(20-29) nanostructures over time, calculate the average thickening speed of small ribbon-like structures, and provide evidence of the coexistence of ribbon and helical fibrils, highlighting a key step within the self-assembly model. In addition, the mutations of individual side chains of wide-type hIAPP(20-29) shift this balance and destabilize the helical fibrils sufficiently relative to the twisted ribbons to lead to their complete elimination. We combine atomic force microscopy structures, mechanical properties, and solid-state NMR structural information to build a molecular model containing β sheets in cross-β motifs as the basis of self-assembled amyloids.",

author = "Shuai Zhang and Maria Andreasen and Nielsen, {Jakob T} and Lei Liu and Nielsen, {Erik H} and Jie Song and Gang Ji and Fei Sun and Troels Skrydstrup and Flemming Besenbacher and Nielsen, {Niels C} and Otzen, {Daniel E} and Mingdong Dong",

year = "2013",

doi = "10.1073/pnas.1209955110",

language = "English",

volume = "110",

pages = "2798--2803",

journal = "Proceedings of the National Academy of Sciences (PNAS)",

issn = "0027-8424",

publisher = "National Academy of Sciences",

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Zhang, S, Andreasen, M, Nielsen, JT, Liu, L, Nielsen, EH, Song, J, Ji, G, Sun, F, Skrydstrup, T, Besenbacher, F, Nielsen, NC , Otzen, DE & Dong, M 2013, 'Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy', Proceedings of the National Academy of Sciences (PNAS), vol. 110, no. 8, pp. 2798-2803. https://doi.org/10.1073/pnas.1209955110

Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy. / Zhang, Shuai; Andreasen, Maria; Nielsen, Jakob T et al.
In: Proceedings of the National Academy of Sciences (PNAS), Vol. 110, No. 8, 2013, p. 2798-2803.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy

AU - Zhang, Shuai

AU - Andreasen, Maria

AU - Nielsen, Jakob T

AU - Liu, Lei

AU - Nielsen, Erik H

AU - Song, Jie

AU - Ji, Gang

AU - Sun, Fei

AU - Skrydstrup, Troels

AU - Besenbacher, Flemming

AU - Nielsen, Niels C

AU - Otzen, Daniel E

AU - Dong, Mingdong

PY - 2013

Y1 - 2013

N2 - Uncontrolled misfolding of proteins leading to the formation of amyloid deposits is associated with more than 40 types of diseases, such as neurodegenerative diseases and type-2 diabetes. These irreversible amyloid fibrils typically assemble in distinct stages. Transitions among the various intermediate stages are the subject of many studies but are not yet fully elucidated. Here, we combine high-resolution atomic force microscopy and quantitative nanomechanical mapping to determine the self-assembled structures of the decapeptide hIAPP(20-29), which is considered to be the fibrillating core fragment of the human islet amyloid polypeptide (hIAPP) involved in type-2 diabetes. We successfully follow the evolution of hIAPP(20-29) nanostructures over time, calculate the average thickening speed of small ribbon-like structures, and provide evidence of the coexistence of ribbon and helical fibrils, highlighting a key step within the self-assembly model. In addition, the mutations of individual side chains of wide-type hIAPP(20-29) shift this balance and destabilize the helical fibrils sufficiently relative to the twisted ribbons to lead to their complete elimination. We combine atomic force microscopy structures, mechanical properties, and solid-state NMR structural information to build a molecular model containing β sheets in cross-β motifs as the basis of self-assembled amyloids.

AB - Uncontrolled misfolding of proteins leading to the formation of amyloid deposits is associated with more than 40 types of diseases, such as neurodegenerative diseases and type-2 diabetes. These irreversible amyloid fibrils typically assemble in distinct stages. Transitions among the various intermediate stages are the subject of many studies but are not yet fully elucidated. Here, we combine high-resolution atomic force microscopy and quantitative nanomechanical mapping to determine the self-assembled structures of the decapeptide hIAPP(20-29), which is considered to be the fibrillating core fragment of the human islet amyloid polypeptide (hIAPP) involved in type-2 diabetes. We successfully follow the evolution of hIAPP(20-29) nanostructures over time, calculate the average thickening speed of small ribbon-like structures, and provide evidence of the coexistence of ribbon and helical fibrils, highlighting a key step within the self-assembly model. In addition, the mutations of individual side chains of wide-type hIAPP(20-29) shift this balance and destabilize the helical fibrils sufficiently relative to the twisted ribbons to lead to their complete elimination. We combine atomic force microscopy structures, mechanical properties, and solid-state NMR structural information to build a molecular model containing β sheets in cross-β motifs as the basis of self-assembled amyloids.

U2 - 10.1073/pnas.1209955110

DO - 10.1073/pnas.1209955110

M3 - Journal article

C2 - 23388629

SN - 0027-8424

VL - 110

SP - 2798

EP - 2803

JO - Proceedings of the National Academy of Sciences (PNAS)

JF - Proceedings of the National Academy of Sciences (PNAS)

IS - 8

ER -

Coexistence of ribbon and helical fibrils originating from hIAPP20-29 revealed by quantitative nanomechanical atomic force microscopy

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