Aarhus University Seal

Dansk

You are here: » Daniel Otzen » Research outputs » The compact and biologically relevant structure of inter-...

About Aarhus University

Daniel Otzen

The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations

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

Standard

The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations. / Scavenius, Carsten; Nikolajsen, Camilla Lund; Stenvang, Marcel et al.

In: Journal of Biological Chemistry, Vol. 291, No. 9, 26.02.2016, p. 4658-4670.

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

Harvard

Scavenius, C, Nikolajsen, CL, Stenvang, M, Thøgersen, I, Wyrozemski, L, Wisniewski, H-G, Otzen, DE, Sanggaard, KW & Enghild, JJ 2016, 'The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations', Journal of Biological Chemistry, vol. 291, no. 9, pp. 4658-4670. https://doi.org/10.1074/jbc.M115.678748

APA

Scavenius, C., Nikolajsen, C. L., Stenvang, M., Thøgersen, I., Wyrozemski, L., Wisniewski, H-G., Otzen, D. E., Sanggaard, K. W., & Enghild, J. J. (2016). The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations. Journal of Biological Chemistry, 291(9), 4658-4670. https://doi.org/10.1074/jbc.M115.678748

CBE

Scavenius C, Nikolajsen CL, Stenvang M, Thøgersen I, Wyrozemski L, Wisniewski H-G, Otzen DE, Sanggaard KW, Enghild JJ. 2016. The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations. Journal of Biological Chemistry. 291(9):4658-4670. https://doi.org/10.1074/jbc.M115.678748

MLA

Scavenius, Carsten et al. "The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations". Journal of Biological Chemistry. 2016, 291(9). 4658-4670. https://doi.org/10.1074/jbc.M115.678748

Vancouver

Scavenius C, Nikolajsen CL, Stenvang M, Thøgersen I, Wyrozemski L, Wisniewski H-G et al. The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations. Journal of Biological Chemistry. 2016 Feb 26;291(9):4658-4670. doi: 10.1074/jbc.M115.678748

Author

Scavenius, Carsten ; Nikolajsen, Camilla Lund ; Stenvang, Marcel et al. / The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 9. pp. 4658-4670.

Bibtex

@article{44b92c20f7984cf4b4c64b0acdf3fab3,
title = "The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations",
abstract = "Inter-α-inhibitor is a proteoglycan of unique structure. The protein consists of three subunits, heavy chain 1, heavy chain 2 and bikunin covalently joined by a chondroitin sulfate chain originating at Ser-10 of bikunin. Inter-α-inhibitor interacts with an inflammation-associated protein, tumor necrosis factor-inducible gene 6 protein, in the extracellular matrix. This interaction leads to transfer of the heavy chains from the chondroitin sulfate of inter-α-inhibitor to hyaluronan and consequently to matrix stabilization. Divalent cations and heavy chain 2 are essential co-factors in this transfer reaction. In the present study, we have investigated how divalent cations in concert with the chondroitin sulfate chain influence the structure and stability of inter-α-inhibitor. The results showed that Mg2+ or Mn2+, but not Ca2+, induced a conformational change in inter-α-inhibitor as evidenced by a decrease in the Stokes radius and a bikunin chondroitin sulfate dependent increase of the thermodynamic stability. This structure was shown to be essential for the ability of inter-α-inhibitor to participate in extracellular matrix stabilization. In addition, the data revealed that bikunin was positioned adjacent to both heavy chains and that the two heavy chains also were in close proximity. The chondroitin sulfate chain interacted with all protein components and inter-α-inhibitor dissociated when it was degraded. Conventional purification protocols result in the removal of the Mg2+ found in plasma and since divalent cations influence the conformation and affect function it is important to consider this when characterizing the biological activity of inter-α-inhibitor.",
author = "Carsten Scavenius and Nikolajsen, {Camilla Lund} and Marcel Stenvang and Ida Th{\o}gersen and Lukasz Wyrozemski and Hans-Georg Wisniewski and Otzen, {Daniel E} and Sanggaard, {Kristian W} and Enghild, {Jan J}",
note = "Copyright {\textcopyright} 2016, The American Society for Biochemistry and Molecular Biology.",
year = "2016",
month = feb,
day = "26",
doi = "10.1074/jbc.M115.678748",
language = "English",
volume = "291",
pages = "4658--4670",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "9",

}

RIS

TY - JOUR

T1 - The compact and biologically relevant structure of inter-α-inhibitor is maintained by the chondroitin sulfate chain and divalent cations

AU - Scavenius, Carsten

AU - Nikolajsen, Camilla Lund

AU - Stenvang, Marcel

AU - Thøgersen, Ida

AU - Wyrozemski, Lukasz

AU - Wisniewski, Hans-Georg

AU - Otzen, Daniel E

AU - Sanggaard, Kristian W

AU - Enghild, Jan J

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

PY - 2016/2/26

Y1 - 2016/2/26

N2 - Inter-α-inhibitor is a proteoglycan of unique structure. The protein consists of three subunits, heavy chain 1, heavy chain 2 and bikunin covalently joined by a chondroitin sulfate chain originating at Ser-10 of bikunin. Inter-α-inhibitor interacts with an inflammation-associated protein, tumor necrosis factor-inducible gene 6 protein, in the extracellular matrix. This interaction leads to transfer of the heavy chains from the chondroitin sulfate of inter-α-inhibitor to hyaluronan and consequently to matrix stabilization. Divalent cations and heavy chain 2 are essential co-factors in this transfer reaction. In the present study, we have investigated how divalent cations in concert with the chondroitin sulfate chain influence the structure and stability of inter-α-inhibitor. The results showed that Mg2+ or Mn2+, but not Ca2+, induced a conformational change in inter-α-inhibitor as evidenced by a decrease in the Stokes radius and a bikunin chondroitin sulfate dependent increase of the thermodynamic stability. This structure was shown to be essential for the ability of inter-α-inhibitor to participate in extracellular matrix stabilization. In addition, the data revealed that bikunin was positioned adjacent to both heavy chains and that the two heavy chains also were in close proximity. The chondroitin sulfate chain interacted with all protein components and inter-α-inhibitor dissociated when it was degraded. Conventional purification protocols result in the removal of the Mg2+ found in plasma and since divalent cations influence the conformation and affect function it is important to consider this when characterizing the biological activity of inter-α-inhibitor.

AB - Inter-α-inhibitor is a proteoglycan of unique structure. The protein consists of three subunits, heavy chain 1, heavy chain 2 and bikunin covalently joined by a chondroitin sulfate chain originating at Ser-10 of bikunin. Inter-α-inhibitor interacts with an inflammation-associated protein, tumor necrosis factor-inducible gene 6 protein, in the extracellular matrix. This interaction leads to transfer of the heavy chains from the chondroitin sulfate of inter-α-inhibitor to hyaluronan and consequently to matrix stabilization. Divalent cations and heavy chain 2 are essential co-factors in this transfer reaction. In the present study, we have investigated how divalent cations in concert with the chondroitin sulfate chain influence the structure and stability of inter-α-inhibitor. The results showed that Mg2+ or Mn2+, but not Ca2+, induced a conformational change in inter-α-inhibitor as evidenced by a decrease in the Stokes radius and a bikunin chondroitin sulfate dependent increase of the thermodynamic stability. This structure was shown to be essential for the ability of inter-α-inhibitor to participate in extracellular matrix stabilization. In addition, the data revealed that bikunin was positioned adjacent to both heavy chains and that the two heavy chains also were in close proximity. The chondroitin sulfate chain interacted with all protein components and inter-α-inhibitor dissociated when it was degraded. Conventional purification protocols result in the removal of the Mg2+ found in plasma and since divalent cations influence the conformation and affect function it is important to consider this when characterizing the biological activity of inter-α-inhibitor.

U2 - 10.1074/jbc.M115.678748

DO - 10.1074/jbc.M115.678748

M3 - Journal article

C2 - 26728454

VL - 291

SP - 4658

EP - 4670

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 9

ER -