Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins

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Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins. / Larsen, Andreas Nørgård; Sørensen, Kasper Kildegaard; Johansen, Nicolai Tidemand; Martel, Anne; Kirkensgaard, Jacob Judas Kain; Jensen, Knud Jørgen; Arleth, Lise; Midtgaard, Søren Roi.

In: Soft Matter, Vol. 12, No. 27, 2016, p. 5937-5949.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Larsen, AN, Sørensen, KK, Johansen, NT, Martel, A, Kirkensgaard, JJK, Jensen, KJ, Arleth, L & Midtgaard, SR 2016, 'Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins', Soft Matter, vol. 12, no. 27, pp. 5937-5949. https://doi.org/10.1039/c6sm00495d

APA

Larsen, A. N., Sørensen, K. K., Johansen, N. T., Martel, A., Kirkensgaard, J. J. K., Jensen, K. J., ... Midtgaard, S. R. (2016). Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins. Soft Matter, 12(27), 5937-5949. https://doi.org/10.1039/c6sm00495d

Vancouver

Larsen AN, Sørensen KK, Johansen NT, Martel A, Kirkensgaard JJK, Jensen KJ et al. Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins. Soft Matter. 2016;12(27):5937-5949. https://doi.org/10.1039/c6sm00495d

Author

Larsen, Andreas Nørgård ; Sørensen, Kasper Kildegaard ; Johansen, Nicolai Tidemand ; Martel, Anne ; Kirkensgaard, Jacob Judas Kain ; Jensen, Knud Jørgen ; Arleth, Lise ; Midtgaard, Søren Roi. / Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins. In: Soft Matter. 2016 ; Vol. 12, No. 27. pp. 5937-5949.

Bibtex

@article{c09540eb649440bfb8e61656f1443e28,
title = "Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins",
abstract = "Three dimers of the amphipathic α-helical peptide 18A have been synthesized with different interhelical linkers inserted between the two copies of 18A. The dimeric peptides were denoted 'beltides' where Beltide-1 refers to the 18A-dimer without a linker, Beltide-2 is the 18A-dimer with proline (Pro) as a linker and Beltide-3 is the 18A-dimer linked by two glycines (Gly-Gly). The self-assembly of the beltides with the phospholipid DMPC was studied with and without the incorporated membrane protein bacteriorhodopsin (bR) through a combination of coarse-grained MD simulations, size-exclusion chromatography (SEC), circular dichroism (CD) spectroscopy, small-angle scattering (SAS), static light scattering (SLS) and UV-Vis spectroscopy. For all three beltides, MD and combined small-angle X-ray and -neutron scattering were consistent with a disc structure composed by a phospholipid bilayer surrounded by a belt of peptides and with a total disc diameter of approximately 10 nm. CD confirmed that all three beltides were α-helical in the free form and with DMPC. However, as shown by SEC the different interhelical linkers clearly led to different properties of the beltides. Beltide-3, with the Gly-Gly linker, was very adaptable such that peptide nanodiscs could be formed for a broad range of different peptide to lipid stoichiometries and therefore also possible disc-sizes. On the other hand, both Beltide-2 with the Pro linker and Beltide-1 without a linker were less adaptable and would only form discs of certain peptide to lipid stoichiometries. SLS revealed that the structural stability of the formed peptide nanodiscs was also highly affected by the linkers and it was found that Beltide-1 gave more stable discs than the other two beltides. With respect to membrane protein stabilization, each of the three beltides in combination with DMPC stabilizes the seven-helix transmembrane protein bacteriorhodopsin significantly better than the detergent octyl glucoside, but no significant difference was observed between the three beltides. We conclude that adaptability, size, and structural stability can be tuned by changing the interhelical linker while maintaining the properties of the discs with respect to membrane protein stabilization.",
author = "Larsen, {Andreas N{\o}rg{\aa}rd} and S{\o}rensen, {Kasper Kildegaard} and Johansen, {Nicolai Tidemand} and Anne Martel and Kirkensgaard, {Jacob Judas Kain} and Jensen, {Knud J{\o}rgen} and Lise Arleth and Midtgaard, {S{\o}ren Roi}",
year = "2016",
doi = "10.1039/c6sm00495d",
language = "English",
volume = "12",
pages = "5937--5949",
journal = "Soft Matter",
issn = "1744-683X",
publisher = "Royal Society of Chemistry",
number = "27",

}

RIS

TY - JOUR

T1 - Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins

AU - Larsen, Andreas Nørgård

AU - Sørensen, Kasper Kildegaard

AU - Johansen, Nicolai Tidemand

AU - Martel, Anne

AU - Kirkensgaard, Jacob Judas Kain

AU - Jensen, Knud Jørgen

AU - Arleth, Lise

AU - Midtgaard, Søren Roi

PY - 2016

Y1 - 2016

N2 - Three dimers of the amphipathic α-helical peptide 18A have been synthesized with different interhelical linkers inserted between the two copies of 18A. The dimeric peptides were denoted 'beltides' where Beltide-1 refers to the 18A-dimer without a linker, Beltide-2 is the 18A-dimer with proline (Pro) as a linker and Beltide-3 is the 18A-dimer linked by two glycines (Gly-Gly). The self-assembly of the beltides with the phospholipid DMPC was studied with and without the incorporated membrane protein bacteriorhodopsin (bR) through a combination of coarse-grained MD simulations, size-exclusion chromatography (SEC), circular dichroism (CD) spectroscopy, small-angle scattering (SAS), static light scattering (SLS) and UV-Vis spectroscopy. For all three beltides, MD and combined small-angle X-ray and -neutron scattering were consistent with a disc structure composed by a phospholipid bilayer surrounded by a belt of peptides and with a total disc diameter of approximately 10 nm. CD confirmed that all three beltides were α-helical in the free form and with DMPC. However, as shown by SEC the different interhelical linkers clearly led to different properties of the beltides. Beltide-3, with the Gly-Gly linker, was very adaptable such that peptide nanodiscs could be formed for a broad range of different peptide to lipid stoichiometries and therefore also possible disc-sizes. On the other hand, both Beltide-2 with the Pro linker and Beltide-1 without a linker were less adaptable and would only form discs of certain peptide to lipid stoichiometries. SLS revealed that the structural stability of the formed peptide nanodiscs was also highly affected by the linkers and it was found that Beltide-1 gave more stable discs than the other two beltides. With respect to membrane protein stabilization, each of the three beltides in combination with DMPC stabilizes the seven-helix transmembrane protein bacteriorhodopsin significantly better than the detergent octyl glucoside, but no significant difference was observed between the three beltides. We conclude that adaptability, size, and structural stability can be tuned by changing the interhelical linker while maintaining the properties of the discs with respect to membrane protein stabilization.

AB - Three dimers of the amphipathic α-helical peptide 18A have been synthesized with different interhelical linkers inserted between the two copies of 18A. The dimeric peptides were denoted 'beltides' where Beltide-1 refers to the 18A-dimer without a linker, Beltide-2 is the 18A-dimer with proline (Pro) as a linker and Beltide-3 is the 18A-dimer linked by two glycines (Gly-Gly). The self-assembly of the beltides with the phospholipid DMPC was studied with and without the incorporated membrane protein bacteriorhodopsin (bR) through a combination of coarse-grained MD simulations, size-exclusion chromatography (SEC), circular dichroism (CD) spectroscopy, small-angle scattering (SAS), static light scattering (SLS) and UV-Vis spectroscopy. For all three beltides, MD and combined small-angle X-ray and -neutron scattering were consistent with a disc structure composed by a phospholipid bilayer surrounded by a belt of peptides and with a total disc diameter of approximately 10 nm. CD confirmed that all three beltides were α-helical in the free form and with DMPC. However, as shown by SEC the different interhelical linkers clearly led to different properties of the beltides. Beltide-3, with the Gly-Gly linker, was very adaptable such that peptide nanodiscs could be formed for a broad range of different peptide to lipid stoichiometries and therefore also possible disc-sizes. On the other hand, both Beltide-2 with the Pro linker and Beltide-1 without a linker were less adaptable and would only form discs of certain peptide to lipid stoichiometries. SLS revealed that the structural stability of the formed peptide nanodiscs was also highly affected by the linkers and it was found that Beltide-1 gave more stable discs than the other two beltides. With respect to membrane protein stabilization, each of the three beltides in combination with DMPC stabilizes the seven-helix transmembrane protein bacteriorhodopsin significantly better than the detergent octyl glucoside, but no significant difference was observed between the three beltides. We conclude that adaptability, size, and structural stability can be tuned by changing the interhelical linker while maintaining the properties of the discs with respect to membrane protein stabilization.

U2 - 10.1039/c6sm00495d

DO - 10.1039/c6sm00495d

M3 - Journal article

C2 - 27306692

AN - SCOPUS:84978120440

VL - 12

SP - 5937

EP - 5949

JO - Soft Matter

JF - Soft Matter

SN - 1744-683X

IS - 27

ER -

ID: 169731675