Heparin binding induces a conformational change in pigment epithelium-derived factor

Zuzana Valnickova; Steen V. Petersen; Søren B. Nielsen; Daniel E. Otzen; Jan J. Enghild

doi:10.1074/jbc.M610471200

Heparin binding induces a conformational change in pigment epithelium-derived factor

Zuzana Valnickova, Steen V. Petersen, Søren B. Nielsen, Daniel E. Otzen, Jan J. Enghild^*

^*Corresponding author for this work

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

22 Citations (Scopus)

Abstract

Pigment epithelium-derived factor (PEDF) is a noninhibitory serpin found in plasma and in the extracellular space. The protein is involved in different biological processes including cell differentiation and survival. In addition, it is a potent inhibitor of angiogenesis. The function is likely associated with binding to cell surface receptors in a heparin-dependent way (Alberdi, E. M., Weldon, J. E., and Becerra, S. P. (2003) BMC Biochem. 4, 1). We have investigated the structural basis for this observation and show that heparin induces a conformational change in the vicinity of Lys¹⁷⁸. This structural change was evident both when binding to intact heparin and specific heparin-derived oligosaccharides at physiological conditions or simply when exposing PEDF to low ionic strength. Binding to other glycosaminoglycans, heparin-derived oligosaccharides smaller than hexadecasaccharides (dp16), or type I collagen did not affect the structure of PEDF. The conformational change is likely to expose the epitope involved in binding to the receptor and thus regulates the interactions with cell surface receptors.

Original language	English
Journal	Journal of Biological Chemistry
Volume	282
Issue	9
Pages (from-to)	6661-6667
Number of pages	7
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M610471200
Publication status	Published - 2 Mar 2007

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title = "Heparin binding induces a conformational change in pigment epithelium-derived factor",

abstract = "Pigment epithelium-derived factor (PEDF) is a noninhibitory serpin found in plasma and in the extracellular space. The protein is involved in different biological processes including cell differentiation and survival. In addition, it is a potent inhibitor of angiogenesis. The function is likely associated with binding to cell surface receptors in a heparin-dependent way (Alberdi, E. M., Weldon, J. E., and Becerra, S. P. (2003) BMC Biochem. 4, 1). We have investigated the structural basis for this observation and show that heparin induces a conformational change in the vicinity of Lys178. This structural change was evident both when binding to intact heparin and specific heparin-derived oligosaccharides at physiological conditions or simply when exposing PEDF to low ionic strength. Binding to other glycosaminoglycans, heparin-derived oligosaccharides smaller than hexadecasaccharides (dp16), or type I collagen did not affect the structure of PEDF. The conformational change is likely to expose the epitope involved in binding to the receptor and thus regulates the interactions with cell surface receptors.",

author = "Zuzana Valnickova and Petersen, {Steen V.} and Nielsen, {S{\o}ren B.} and Otzen, {Daniel E.} and Enghild, {Jan J.}",

year = "2007",

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doi = "10.1074/jbc.M610471200",

language = "English",

volume = "282",

pages = "6661--6667",

journal = "Journal of Biological Chemistry",

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Heparin binding induces a conformational change in pigment epithelium-derived factor. / Valnickova, Zuzana; Petersen, Steen V.; Nielsen, Søren B. et al.
In: Journal of Biological Chemistry, Vol. 282, No. 9, 02.03.2007, p. 6661-6667.

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

TY - JOUR

T1 - Heparin binding induces a conformational change in pigment epithelium-derived factor

AU - Valnickova, Zuzana

AU - Petersen, Steen V.

AU - Nielsen, Søren B.

AU - Otzen, Daniel E.

AU - Enghild, Jan J.

PY - 2007/3/2

Y1 - 2007/3/2

N2 - Pigment epithelium-derived factor (PEDF) is a noninhibitory serpin found in plasma and in the extracellular space. The protein is involved in different biological processes including cell differentiation and survival. In addition, it is a potent inhibitor of angiogenesis. The function is likely associated with binding to cell surface receptors in a heparin-dependent way (Alberdi, E. M., Weldon, J. E., and Becerra, S. P. (2003) BMC Biochem. 4, 1). We have investigated the structural basis for this observation and show that heparin induces a conformational change in the vicinity of Lys178. This structural change was evident both when binding to intact heparin and specific heparin-derived oligosaccharides at physiological conditions or simply when exposing PEDF to low ionic strength. Binding to other glycosaminoglycans, heparin-derived oligosaccharides smaller than hexadecasaccharides (dp16), or type I collagen did not affect the structure of PEDF. The conformational change is likely to expose the epitope involved in binding to the receptor and thus regulates the interactions with cell surface receptors.

AB - Pigment epithelium-derived factor (PEDF) is a noninhibitory serpin found in plasma and in the extracellular space. The protein is involved in different biological processes including cell differentiation and survival. In addition, it is a potent inhibitor of angiogenesis. The function is likely associated with binding to cell surface receptors in a heparin-dependent way (Alberdi, E. M., Weldon, J. E., and Becerra, S. P. (2003) BMC Biochem. 4, 1). We have investigated the structural basis for this observation and show that heparin induces a conformational change in the vicinity of Lys178. This structural change was evident both when binding to intact heparin and specific heparin-derived oligosaccharides at physiological conditions or simply when exposing PEDF to low ionic strength. Binding to other glycosaminoglycans, heparin-derived oligosaccharides smaller than hexadecasaccharides (dp16), or type I collagen did not affect the structure of PEDF. The conformational change is likely to expose the epitope involved in binding to the receptor and thus regulates the interactions with cell surface receptors.

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DO - 10.1074/jbc.M610471200

M3 - Journal article

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AN - SCOPUS:34250347338

SN - 0021-9258

VL - 282

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EP - 6667

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 9

ER -

Heparin binding induces a conformational change in pigment epithelium-derived factor

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