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Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin

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Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin. / Christensen, Brian; Zachariae, Elias D; Scavenius, Carsten et al.

In: Biochemistry, Vol. 55, No. 2, 19.01.2016, p. 294-303.

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

Harvard

Christensen, B, Zachariae, ED, Scavenius, C, Kløverpris, S, Oxvig, C, Petersen, SV, Enghild, JJ & Sørensen, ES 2016, 'Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin', Biochemistry, vol. 55, no. 2, pp. 294-303. https://doi.org/10.1021/acs.biochem.5b01153

APA

Christensen, B., Zachariae, E. D., Scavenius, C., Kløverpris, S., Oxvig, C., Petersen, S. V., Enghild, J. J., & Sørensen, E. S. (2016). Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin. Biochemistry, 55(2), 294-303. https://doi.org/10.1021/acs.biochem.5b01153

CBE

Christensen B, Zachariae ED, Scavenius C, Kløverpris S, Oxvig C, Petersen SV, Enghild JJ, Sørensen ES. 2016. Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin. Biochemistry. 55(2):294-303. https://doi.org/10.1021/acs.biochem.5b01153

MLA

Christensen, Brian et al. "Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin". Biochemistry. 2016, 55(2). 294-303. https://doi.org/10.1021/acs.biochem.5b01153

Vancouver

Christensen B, Zachariae ED, Scavenius C, Kløverpris S, Oxvig C, Petersen SV et al. Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin. Biochemistry. 2016 Jan 19;55(2):294-303. doi: 10.1021/acs.biochem.5b01153

Author

Christensen, Brian ; Zachariae, Elias D ; Scavenius, Carsten et al. / Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin. In: Biochemistry. 2016 ; Vol. 55, No. 2. pp. 294-303.

Bibtex

@article{8f4a237d235c4977b6edbece95ef4097,
title = "Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin",
abstract = "Osteopontin (OPN) is a multifunctional integrin-binding protein present in several tissues and body fluids. OPN is a substrate for the enzyme transglutaminase 2 (TG2), which catalyzes inter- and intramolecular cross-linking affecting the biological activity of the protein. Polymerization of OPN by intermolecular cross-linking has mostly been studied using relatively high TG2 concentrations, whereas the effect of lower concentrations of TG2 has remained unexplored. Here we show that TG2 at physiologically relevant concentrations predominantly catalyzes the formation of intramolecular cross-links in OPN. By site-directed mutagenesis and mass spectrometry, we demonstrate that Gln(42) and Gln(193) serve as the primary amine acceptor sites for isopeptide bond formation. We find that Gln(42) predominantly is linked to Lys(4) and that Gln(193) participates in a cross-link with Lys(154), Lys(157), or Lys(231). The formation of specific isopeptide bonds was not dependent on OPN phosphorylation, and similar patterns of cross-linking were observed in human and mouse OPN. Furthermore, we find that OPN purified from human urine contains the Lys(154)-Gln(193) isopeptide bond, indicating that intramolecular cross-linking of OPN occurs in vivo. Collectively, these data suggest that specific intramolecular cross-linking in the N- and C-terminal parts of OPN is most likely the dominant step in TG2-catalyzed modification of OPN.",
author = "Brian Christensen and Zachariae, {Elias D} and Carsten Scavenius and S{\o}ren Kl{\o}verpris and Claus Oxvig and Petersen, {Steen V} and Enghild, {Jan J} and S{\o}rensen, {Esben S}",
year = "2016",
month = jan,
day = "19",
doi = "10.1021/acs.biochem.5b01153",
language = "English",
volume = "55",
pages = "294--303",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "ACS Publications",
number = "2",

}

RIS

TY - JOUR

T1 - Transglutaminase 2-Catalyzed Intramolecular Cross-Linking of Osteopontin

AU - Christensen, Brian

AU - Zachariae, Elias D

AU - Scavenius, Carsten

AU - Kløverpris, Søren

AU - Oxvig, Claus

AU - Petersen, Steen V

AU - Enghild, Jan J

AU - Sørensen, Esben S

PY - 2016/1/19

Y1 - 2016/1/19

N2 - Osteopontin (OPN) is a multifunctional integrin-binding protein present in several tissues and body fluids. OPN is a substrate for the enzyme transglutaminase 2 (TG2), which catalyzes inter- and intramolecular cross-linking affecting the biological activity of the protein. Polymerization of OPN by intermolecular cross-linking has mostly been studied using relatively high TG2 concentrations, whereas the effect of lower concentrations of TG2 has remained unexplored. Here we show that TG2 at physiologically relevant concentrations predominantly catalyzes the formation of intramolecular cross-links in OPN. By site-directed mutagenesis and mass spectrometry, we demonstrate that Gln(42) and Gln(193) serve as the primary amine acceptor sites for isopeptide bond formation. We find that Gln(42) predominantly is linked to Lys(4) and that Gln(193) participates in a cross-link with Lys(154), Lys(157), or Lys(231). The formation of specific isopeptide bonds was not dependent on OPN phosphorylation, and similar patterns of cross-linking were observed in human and mouse OPN. Furthermore, we find that OPN purified from human urine contains the Lys(154)-Gln(193) isopeptide bond, indicating that intramolecular cross-linking of OPN occurs in vivo. Collectively, these data suggest that specific intramolecular cross-linking in the N- and C-terminal parts of OPN is most likely the dominant step in TG2-catalyzed modification of OPN.

AB - Osteopontin (OPN) is a multifunctional integrin-binding protein present in several tissues and body fluids. OPN is a substrate for the enzyme transglutaminase 2 (TG2), which catalyzes inter- and intramolecular cross-linking affecting the biological activity of the protein. Polymerization of OPN by intermolecular cross-linking has mostly been studied using relatively high TG2 concentrations, whereas the effect of lower concentrations of TG2 has remained unexplored. Here we show that TG2 at physiologically relevant concentrations predominantly catalyzes the formation of intramolecular cross-links in OPN. By site-directed mutagenesis and mass spectrometry, we demonstrate that Gln(42) and Gln(193) serve as the primary amine acceptor sites for isopeptide bond formation. We find that Gln(42) predominantly is linked to Lys(4) and that Gln(193) participates in a cross-link with Lys(154), Lys(157), or Lys(231). The formation of specific isopeptide bonds was not dependent on OPN phosphorylation, and similar patterns of cross-linking were observed in human and mouse OPN. Furthermore, we find that OPN purified from human urine contains the Lys(154)-Gln(193) isopeptide bond, indicating that intramolecular cross-linking of OPN occurs in vivo. Collectively, these data suggest that specific intramolecular cross-linking in the N- and C-terminal parts of OPN is most likely the dominant step in TG2-catalyzed modification of OPN.

U2 - 10.1021/acs.biochem.5b01153

DO - 10.1021/acs.biochem.5b01153

M3 - Journal article

C2 - 26678563

VL - 55

SP - 294

EP - 303

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 2

ER -