We used ELISA and flow cytometry to study the binding of prion protein PrP to glycosaminoglycans (GAGs). We found that recombinant human PrP (rPrP) binds GAGs including chondroitin sulphate A, chondroitin sulphate B, hyaluronic acid, and heparin. rPrP binding to GAGs occurs via the N-terminus, a region known to bind divalent cations. Additionally, rPrP binding to GAGs is enhanced in the presence of Cu2+ and Zn2+, but not Ca2+ and Mn2+. rPrP binds heparin strongest, and the binding is inhibited by certain heparin analogues, including heparin disaccharide and sulphate-containing monosaccharides, but not by acetylated heparin. Full-length normal cellular prion protein (PrPC), but not N-terminally truncated PrPC species, from human brain bind GAGs in a similar Cu2+/Zn2+-enhanced fashion. We found that GAGs specifically bind to a synthetic peptide corresponding to amino acid residues 23—35 in the N-terminus of rPrP. We further demonstrated that while both wild-type PrPC and an octapeptide-repeat-deleted mutant PrP produced by transfected cells bound heparin at the cell surface, the PrP N-terminal deletion mutant and non-transfectant control failed to bind heparin. Binding of heparin to wild-type PrPC on the cell surface results in a reduction of the level of cell-surface PrPC. These results provide strong evidence that PrPC is a surface receptor for GAGs.
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November 2002
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Research Article|
November 15 2002
Cell-surface prion protein interacts with glycosaminoglycans Available to Purchase
Tao PAN;
Tao PAN
∗Institute of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-1712, U.S.A.,
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Boon-Seng WONG;
Boon-Seng WONG
∗Institute of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-1712, U.S.A.,
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Tong LIU;
Tong LIU
∗Institute of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-1712, U.S.A.,
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Ruliang LI;
Ruliang LI
∗Institute of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-1712, U.S.A.,
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Robert B. PETERSEN;
Robert B. PETERSEN
∗Institute of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-1712, U.S.A.,
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Man-Sun SY
Man-Sun SY
1
†Institute of Pathology, Cancer Research Center, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-1712, U.S.A.
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
May 14 2002
Revision Received:
July 19 2002
Accepted:
August 20 2002
Accepted Manuscript online:
August 20 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 368 (1): 81–90.
Article history
Received:
May 14 2002
Revision Received:
July 19 2002
Accepted:
August 20 2002
Accepted Manuscript online:
August 20 2002
Citation
Tao PAN, Boon-Seng WONG, Tong LIU, Ruliang LI, Robert B. PETERSEN, Man-Sun SY; Cell-surface prion protein interacts with glycosaminoglycans. Biochem J 15 November 2002; 368 (1): 81–90. doi: https://doi.org/10.1042/bj20020773
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