Aarhus University Seal

Daniel Otzen

How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. / Malmos, Kirsten G; Bjerring, Morten; Jessen, Christian Moestrup et al.

In: Journal of Biological Chemistry, Vol. 291, No. 32, 05.08.2016, p. 16849-16862.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Malmos, KG, Bjerring, M, Jessen, CM, Nielsen, EHT, Poulsen, ET, Christiansen, G, Vosegaard, T, Skrydstrup, T, Enghild, JJ, Pedersen, JS & Otzen, DE 2016, 'How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin', Journal of Biological Chemistry, vol. 291, no. 32, pp. 16849-16862. https://doi.org/10.1074/jbc.M116.715466

APA

Malmos, K. G., Bjerring, M., Jessen, C. M., Nielsen, E. H. T., Poulsen, E. T., Christiansen, G., Vosegaard, T., Skrydstrup, T., Enghild, J. J., Pedersen, J. S., & Otzen, D. E. (2016). How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. Journal of Biological Chemistry, 291(32), 16849-16862. https://doi.org/10.1074/jbc.M116.715466

CBE

Malmos KG, Bjerring M, Jessen CM, Nielsen EHT, Poulsen ET, Christiansen G, Vosegaard T, Skrydstrup T, Enghild JJ, Pedersen JS, et al. 2016. How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. Journal of Biological Chemistry. 291(32):16849-16862. https://doi.org/10.1074/jbc.M116.715466

MLA

Malmos, Kirsten G et al. "How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin". Journal of Biological Chemistry. 2016, 291(32). 16849-16862. https://doi.org/10.1074/jbc.M116.715466

Vancouver

Malmos KG, Bjerring M, Jessen CM, Nielsen EHT, Poulsen ET, Christiansen G et al. How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. Journal of Biological Chemistry. 2016 Aug 5;291(32):16849-16862. doi: 10.1074/jbc.M116.715466

Author

Malmos, Kirsten G ; Bjerring, Morten ; Jessen, Christian Moestrup et al. / How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 32. pp. 16849-16862.

Bibtex

@article{41251d991409422aa21b92a0218962d4,
title = "How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin",
abstract = "Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAGs interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3-7. SAXS indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT:heparin complexes form β-sheet rich heparin-covered fibrils. Solid state NMR reveals that heparin does not alter the sCT fibrillary core around Lys11 but makes changes to Val8 on the exterior side of the β-strand, possibly through contacts to Lys18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting both with monomeric and aggregated sCT.",
author = "Malmos, {Kirsten G} and Morten Bjerring and Jessen, {Christian Moestrup} and Nielsen, {Erik Holm Toustrup} and Poulsen, {Ebbe Toftgaard} and Gunna Christiansen and Thomas Vosegaard and Troels Skrydstrup and Enghild, {Jan J} and Pedersen, {Jan Skov} and Otzen, {Daniel E}",
note = "Copyright {\textcopyright} 2016, The American Society for Biochemistry and Molecular Biology.",
year = "2016",
month = aug,
day = "5",
doi = "10.1074/jbc.M116.715466",
language = "English",
volume = "291",
pages = "16849--16862",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "32",

}

RIS

TY - JOUR

T1 - How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin

AU - Malmos, Kirsten G

AU - Bjerring, Morten

AU - Jessen, Christian Moestrup

AU - Nielsen, Erik Holm Toustrup

AU - Poulsen, Ebbe Toftgaard

AU - Christiansen, Gunna

AU - Vosegaard, Thomas

AU - Skrydstrup, Troels

AU - Enghild, Jan J

AU - Pedersen, Jan Skov

AU - Otzen, Daniel E

N1 - Copyright © 2016, The American Society for Biochemistry and Molecular Biology.

PY - 2016/8/5

Y1 - 2016/8/5

N2 - Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAGs interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3-7. SAXS indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT:heparin complexes form β-sheet rich heparin-covered fibrils. Solid state NMR reveals that heparin does not alter the sCT fibrillary core around Lys11 but makes changes to Val8 on the exterior side of the β-strand, possibly through contacts to Lys18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting both with monomeric and aggregated sCT.

AB - Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAGs interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3-7. SAXS indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT:heparin complexes form β-sheet rich heparin-covered fibrils. Solid state NMR reveals that heparin does not alter the sCT fibrillary core around Lys11 but makes changes to Val8 on the exterior side of the β-strand, possibly through contacts to Lys18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting both with monomeric and aggregated sCT.

U2 - 10.1074/jbc.M116.715466

DO - 10.1074/jbc.M116.715466

M3 - Journal article

C2 - 27281819

VL - 291

SP - 16849

EP - 16862

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 32

ER -