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Divalent metal binding by histidine‐rich glycoprotein differentially regulates higher order oligomerisation and proteolytic processing
Author(s) -
Priebatsch Kristin M.,
Poon Ivan K. H.,
Patel Kruti K.,
Kvansakul Marc,
Hulett Mark D.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12520
Subject(s) - histidine , glycoprotein , chemistry , divalent , biochemistry , divalent metal , metal , amino acid , organic chemistry
The serum protein histidine‐rich glycoprotein ( HRG ) has been implicated in tissue injury and tumour growth. Several HRG functions are regulated by the divalent metal Zn 2+ , including ligand binding and proteolytic processing that releases active HRG fragments. Although HRG can bind divalent metals other than Zn 2+ , the impact of these divalent metals on the biophysical properties of HRG remains poorly understood. We now show that HRG binds Zn 2+ , Ni 2+ , Cu 2+ and Co 2+ with micromolar affinities, but differing stoichiometries, and regulate the release of specific HRG fragments during proteolysis. Furthermore, HRG binding to Zn 2+ promotes HRG dimer formation in a Zn 2+ ‐concentration‐ and pH‐dependent manner. Our data highlight the complex divalent metal‐dependent regulatory mechanisms that govern HRG function.