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Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance

Publication ,  Journal Article
Kim, SY; Zhang, F; Harris, DA; Linhardt, RJ
Published in: Frontiers in Molecular Biosciences
November 26, 2020

Self-propagating form of the prion protein (PrPSc) causes many neurodegenerative diseases, such as Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker syndrome (GSS). Heparin is a highly sulfated linear glycosaminoglycan (GAG) and is composed of alternating D-glucosamine and L-iduronic acid or D-glucuronic acid sugar residues. The interactions of heparin with various proteins in a domain-specific or charged-dependent manner provide key roles on many physiological and pathological processes. While GAG-PrP interactions had been previously reported, the specific glycan structures that facilitate interactions with different regions of PrP and their binding kinetics have not been systematically investigated. In this study, we performed direct binding surface plasmon resonance (SPR) assay to characterize the kinetics of heparin binding to four recombinant murine PrP constructs including full length (M23–230), a deletion mutant lacking the four histidine-containing octapeptide repeats (M23–230 Δ59–90), the isolated N-terminal domain (M23–109), and the isolated C-terminal domain (M90–230). Additionally, we found the specific structural determinants required for GAG binding to the four PrP constructs with chemically defined derivatives of heparin and other GAGs by an SPR competition assay. Our findings may be instrumental in developing designer GAGs for specific targets within the PrP to fine-tune biological and pathophysiological activities of PrP.

Duke Scholars

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Published In

Frontiers in Molecular Biosciences

DOI

EISSN

2296-889X

Publication Date

November 26, 2020

Volume

7

Related Subject Headings

  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
 

Citation

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Kim, S. Y., Zhang, F., Harris, D. A., & Linhardt, R. J. (2020). Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance. Frontiers in Molecular Biosciences, 7. https://doi.org/10.3389/fmolb.2020.594497
Kim, S. Y., F. Zhang, D. A. Harris, and R. J. Linhardt. “Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance.” Frontiers in Molecular Biosciences 7 (November 26, 2020). https://doi.org/10.3389/fmolb.2020.594497.
Kim SY, Zhang F, Harris DA, Linhardt RJ. Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance. Frontiers in Molecular Biosciences. 2020 Nov 26;7.
Kim, S. Y., et al. “Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance.” Frontiers in Molecular Biosciences, vol. 7, Nov. 2020. Scopus, doi:10.3389/fmolb.2020.594497.
Kim SY, Zhang F, Harris DA, Linhardt RJ. Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance. Frontiers in Molecular Biosciences. 2020 Nov 26;7.

Published In

Frontiers in Molecular Biosciences

DOI

EISSN

2296-889X

Publication Date

November 26, 2020

Volume

7

Related Subject Headings

  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology