A novel mechanism for protein delivery: Granzyme B undergoes electrostatic exchange from serglycin to target cells

Srikumar M. Raja*, Sunil S. Metkar, Stefan Höning, Baikun Wang, William A. Russin, Nina H. Pipalia, Cheikh Menaa, Mattias Belting, Xuefang Cao, Ralf Dressel, Christopher J. Froelich

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The molecular interaction of secreted granzyme B-serglycin complexes with target cells remains undefined. Targets exposed to double-labeled granzyme B-serglycin complexes show solely the uptake of granzyme B. An in vitro model demonstrates the exchange of the granzyme from serglycin to immobilized, sulfated glycosaminoglycans. Using a combination of cell binding and internalization assays, granzyme B was found to exchange to sulfated glycosaminoglycans and, depending on the cell type, to higher affinity sites. Apoptosis induced by purified granzyme B and cytotoxic T-cells was diminished in targets with reduced cell surface glycosaminoglycan content. A mechanism of delivery is proposed entailing electrostatic transfer of granzyme B from serglycin to cell surface proteins.

Original languageEnglish (US)
Pages (from-to)20752-20761
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number21
DOIs
StatePublished - May 27 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Raja, S. M., Metkar, S. S., Höning, S., Wang, B., Russin, W. A., Pipalia, N. H., Menaa, C., Belting, M., Cao, X., Dressel, R., & Froelich, C. J. (2005). A novel mechanism for protein delivery: Granzyme B undergoes electrostatic exchange from serglycin to target cells. Journal of Biological Chemistry, 280(21), 20752-20761. https://doi.org/10.1074/jbc.M501181200