Divalent metal binding by histidine-rich glycoprotein differentially regulates higher order oligomerisation and proteolytic processing

作者：Priebatsch Kristin M; Poon Ivan K H; Patel Kruti K; Kvansakul Marc; Hulett Mark D

来源：FEBS LETTERS, 2017, 591(1): 164-176.

DOI：10.1002/1873-3468.12520

• divalent metals
• histidine-rich glycoprotein
• zinc

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 Zn2+, including ligand binding and proteolytic processing that releases active HRG fragments. Although HRG can bind divalent metals other than Zn2+, the impact of these divalent metals on the biophysical properties of HRG remains poorly understood. We now show that HRG binds Zn2+, Ni2+, Cu2+ and Co2+ with micromolar affinities, but differing stoichiometries, and regulate the release of specific HRG fragments during proteolysis. Furthermore, HRG binding to Zn2+ promotes HRG dimer formation in a Zn2+-concentration-and pH-dependent manner. Our data highlight the complex divalent metal-dependent regulatory mechanisms that govern HRG function.

• 出版日期2017-1