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 af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

22 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Biological Chemistry
Vol/bind	282
Nummer	9
Sider (fra-til)	6661-6667
Antal sider	7
ISSN	0021-9258
DOI	https://doi.org/10.1074/jbc.M610471200
Status	Udgivet - 2 mar. 2007

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Citationsformater

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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.}",

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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.

UR - http://www.scopus.com/inward/record.url?scp=34250347338&partnerID=8YFLogxK

U2 - 10.1074/jbc.M610471200

DO - 10.1074/jbc.M610471200

M3 - Journal article

C2 - 17202143

AN - SCOPUS:34250347338

SN - 0021-9258

VL - 282

SP - 6661

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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