Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface

Karsten Buschard; Austin W. Bracey; Daniel L. McElroy; Andrew T. Magis; Thomas Osterbye; Mark A. Atkinson; Kate M. Bailey; Amanda L. Posgai; David A Ostrov

doi:10.1155/2016/6179635

Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface

Karsten Buschard^*, Austin W. Bracey, Daniel L. McElroy, Andrew T. Magis, Thomas Osterbye, Mark A. Atkinson, Kate M. Bailey, Amanda L. Posgai, David A Ostrov

^*Corresponding author for this work

5 Citations (Scopus)

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Abstract

Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. Conclusions. Sulfatide is known to stabilize insulin crystals, and we demonstrate here that in beta cells sulfatide is likely coating insulin crystals. However, there is no evidence for sulfatide to be built into the crystal lattice.

Original language	English
Article number	6179635
Journal	Journal of Diabetes Research
Volume	2016
Number of pages	5
ISSN	2314-6745
DOIs	https://doi.org/10.1155/2016/6179635
Publication status	Published - 2016

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Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their SurfaceFinal published version, 1.7 MBLicence: CC BY

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@article{5c8fcc5b659c45b3b4d9697cd53ad02c,

title = "Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface",

abstract = "Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. Conclusions. Sulfatide is known to stabilize insulin crystals, and we demonstrate here that in beta cells sulfatide is likely coating insulin crystals. However, there is no evidence for sulfatide to be built into the crystal lattice.",

author = "Karsten Buschard and Bracey, {Austin W.} and McElroy, {Daniel L.} and Magis, {Andrew T.} and Thomas Osterbye and Atkinson, {Mark A.} and Bailey, {Kate M.} and Posgai, {Amanda L.} and Ostrov, {David A}",

year = "2016",

doi = "10.1155/2016/6179635",

language = "English",

volume = "2016",

journal = "Journal of Diabetes Research",

issn = "2314-6745",

publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface

AU - Buschard, Karsten

AU - Bracey, Austin W.

AU - McElroy, Daniel L.

AU - Magis, Andrew T.

AU - Osterbye, Thomas

AU - Atkinson, Mark A.

AU - Bailey, Kate M.

AU - Posgai, Amanda L.

AU - Ostrov, David A

PY - 2016

Y1 - 2016

N2 - Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. Conclusions. Sulfatide is known to stabilize insulin crystals, and we demonstrate here that in beta cells sulfatide is likely coating insulin crystals. However, there is no evidence for sulfatide to be built into the crystal lattice.

AB - Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. Conclusions. Sulfatide is known to stabilize insulin crystals, and we demonstrate here that in beta cells sulfatide is likely coating insulin crystals. However, there is no evidence for sulfatide to be built into the crystal lattice.

U2 - 10.1155/2016/6179635

DO - 10.1155/2016/6179635

M3 - Journal article

C2 - 26981544

AN - SCOPUS:84959258711

SN - 2314-6745

VL - 2016

JO - Journal of Diabetes Research

JF - Journal of Diabetes Research

M1 - 6179635

ER -

Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface

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