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Glycobiology Advance Access first published online on August 2, 2007
This version published online on August 17, 2007
Glycobiology, doi:10.1093/glycob/cwm082
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Binding of Human Betacellulin to Heparin, Heparan Sulphate and Related Polysaccharides

Rosemary S. Mummery, Barbara Mulloy and Christopher C. Rider

School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 OEX, UK
Laboratory for Molecular Structure, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts, EN6 3QG, UK

Corresponding author to whom proofs and reprints should be addressed: Dr C. C. Rider, email: c.rider{at}rhul.ac.uk, Tel: +44-(0)1784-443548, Fax: +44-(0)1784-414224

Received on April 26, 2007; accepted on July 27, 2007

Recombinant human betacellulin binds strongly to heparin, requiring of the order of 0.8M NaCl for its elution from a heparin affinity matrix. This is in complete contrast to the prototypic member of its cytokine superfamily, epidermal growth factor, which fails to bind to the column at physiological pH and strength. We used a well-established heparin binding ELISA to demonstrate that fucoidan and a highly sulphated variant of heparan sulphate compete strongly for heparin binding. Low sulphated heparan sulphates and also chondroitin sulphates are weaker competitors. Moreover, although competitive activity is reduced by selective desulphation, residual binding to extensively desulphated heparin remains. Even carboxyl reduction followed by extensive desulphation does not completely remove activity. We further demonstrate that both hyaluronic acid and the E. coli capsular polysaccharide K5, both of which are unsulphated polysaccharides with unbranched chains of alternating N-acetyl glucosamine linked ß(1-4) to glucuronic acid, are also capable of a limited degree of competition with heparin. Heparin protects betacellulin from proteolysis by LysC, but K5 polysaccharide does not. Betacellulin possesses a prominent cluster of basic residues which is likely to constitute a binding site for sulphated polysaccharides, but the binding of non-sulphated polysaccharides may take place at a different site.

Key words: betacellulin / heparin / heparan sulphate / glycosaminoglycan / polysaccharides


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