Investigating native metal ion binding sites in mammalian histidine-rich glycoprotein

Katrin Ackermann, Siavash Khazaipoul, Joshua Wort, Amelie Isabelle Sylvie Sobczak, Hassane El Mkami, Alan J. Stewart*, Bela Ernest Bode*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
9 Downloads (Pure)


Mammalian histidine-rich glycoprotein (HRG) is a highly versatile and abundant blood plasma glycoprotein with a diverse range of ligands that is involved in regulating many essential biological processes, including coagulation, cell adhesion, and angiogenesis. Despite its biomedical importance, structural information on the multi-domain protein is sparse, not least due to intrinsically disordered regions that elude high-resolution structural characterization. Binding of divalent metal ions, particularly ZnII, to multiple sites within the HRG protein is of critical functional importance and exerts a regulatory role. However, characterization of the ZnII binding sites of HRG is a challenge; their number and composition as well as their affinities and stoichiometries of binding are currently not fully understood. In this study, we explored modern electron paramagnetic resonance (EPR) spectroscopy methods supported by protein secondary and tertiary structure prediction to assemble a holistic picture of native HRG and its interaction with metal ions. To the best of our knowledge, this is the first time that this suite of EPR techniques has been applied to count and characterize endogenous metal ion binding sites in a native mammalian protein of unknown structure.
Original languageEnglish
Pages (from-to)8064-8072
Number of pages9
JournalJournal of the American Chemical Society
Issue number14
Early online date31 Mar 2023
Publication statusPublished - 12 Apr 2023


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