title: Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+in Settings of Tissue Injury.
abstract: Divalent metal ions are essential nutrients for all living organisms and are commonly protein-bound where they perform important roles in protein structure and function. This regulatory control from metals is observed in the relatively abundant plasma protein histidine-rich glycoprotein (HRG), which displays preferential binding to the second most abundant transition element in human systems, Zinc (Zn2+). HRG has been proposed to interact with a large number of protein ligands and has been implicated in the regulation of various physiological and pathological processes including the formation of immune complexes, apoptotic/necrotic and pathogen clearance, cell adhesion, antimicrobial activity, angiogenesis, coagulation and fibrinolysis. Interestingly, these processes are often associated with sites of tissue injury or tumour growth, where the concentration and distribution of Zn2+is known to vary. Changes in Zn2+levels have been shown to modify HRG function by altering its affinity for certain ligands and/or providing protection against proteolytic disassembly by serine proteases. This review focuses on the molecular interplay between HRG and Zn2+, and how Zn2+binding modifies HRG-ligand interactions to regulate function in different settings of tissue injury.
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. kmpriebatsch@students.latrobe.edu.au.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Priebatsch
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. m.kvansakul@latrobe.edu.au.
authors.forename: Marc
authors.initials: M
authors.lastname: Kvansakul
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. I.Poon@latrobe.edu.au.
authors.forename: Ivan K H
authors.initials: IK
authors.lastname: Poon
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. m.hulett@latrobe.edu.au.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hulett
mesh_terms: D000818:Animals; D017209:Apoptosis; D001798:Blood Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009928:Organ Specificity; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*; D000099053:Histidine-Rich Glycoprotein
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D015032:Zinc
keywords: cancer; histidine-rich glycoprotein; plasma protein; tissue injury; wound healing; zinc