Direct Measurement of the Interaction of Glycosaminoglycans and a Heparin Decasaccharide with Malaria Circumsporozoite Protein

Authors
Rathore, D.
McCutchan, T.F.
Hernaiz, M.J.
LeBrun, L.A.
Lang, S.C.
Linhardt, Robert J.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2001-09-25
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Direct Measurement of the Interaction of Glycosaminoglycans and a Heparin Decasaccharide with Malaria Circumsporozoite Protein, D. Rathore, T. F. McCutchan, M. J. Hernaiz, L.A. LeBrun, S.C. Lang, R.J. Linhardt, Biochemistry, 40, 11518-11524, 2001.
Abstract
Circumsporozoite (CS) protein is a predominant surface antigen of malaria sporozoites, the infective form of the parasite, and has been used for making anti-malaria vaccines. For the first time we have examined the interaction of CS protein with various glycosaminoglycans in real time using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Heparin was the best binder among the glycosaminoglycans tested and bound to CS protein with nanomolar affinity. Using purified and structurally defined small heparin oligosaccharides, we identified a decasaccharide to be the minimum sized CS protein-binding sequence. In an indirect competition assay, this decasaccharide blocked the CS protein interaction with HepG2 cells with an ID50 of less than 60 nM. The decasaccharide has a structure commonly found in hepatic heparan sulfate, and the same sequence has recently been shown to bind specifically to apolipoprotein E. Examination of porcine liver heparan sulfate in this indirect competition assay showed that it and heparin were the only glycosaminoglycans that could effectively block CS protein interaction with HepG2 cells in culture. These data support the hypothesis that the invasion of liver cells by the parasite shares a common mechanism with the hepatic uptake of lipoprotein remnants from the blood.
Description
Biochemistry, 40, 11518-11524
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemistry
https://harc.rpi.edu/
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