Probing the Cu2+ and Zn2+ binding affinity of histidine-rich glycoprotein

Jancsó, Attila; Kolozsi, András; Gyurcsik, Béla; Nagy, Nóra Veronika; Gajda, Tamás

doi:10.1016/j.jinorgbio.2009.09.002

Cited by 35 publications

(34 citation statements)

References 61 publications

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“…Therefore, Zn 2ϩ may act as a cofactor that simultaneously binds HRG and fibrin(ogen) in a coordinated fashion (39). Alternatively, Zn 2ϩ binding to HRG may induce conformational changes that facilitate its interaction with fibrin(ogen), a concept supported by the observation that Zn 2ϩ alters the conformation of a synthetic His-Pro-rich peptide (16 (15,40). These data point to a mechanism whereby Zn 2ϩ modulates the structure and function of HRG.…”

Section: Discussionmentioning

confidence: 97%

“…A 75-kDa glycoprotein, HRG, is composed of two NH 2 -terminal cystatin-like domains, a central histidine-rich region (HRR) flanked by two prolinerich regions, and a COOH-terminal domain (14). In addition to fibrinogen, HRG also binds plasminogen, heparan sulfate, and divalent cations, such as Zn 2ϩ (12,15,16). Therefore, HRG is hypothesized to be an important accessory or adapter protein that brings different ligands together under specific conditions (14).…”

Section: Histidine-rich Glycoprotein (Hrg) Is An Abundant Protein Thamentioning

confidence: 99%

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Histidine-rich Glycoprotein Binds Fibrin(ogen) with High Affinity and Competes with Thrombin for Binding to the γ′-Chain

Stafford

Leslie

et al. 2011

Journal of Biological Chemistry

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Histidine-rich glycoprotein (HRG) is an abundant protein that binds fibrinogen and other plasma proteins in a Zn2؉ -dependent fashion but whose function is unclear. HRG has antimicrobial activity, and its incorporation into fibrin clots facilitates bacterial entrapment and killing and promotes inflammation. Although these findings suggest that HRG contributes to innate immunity and inflammation, little is known about the HRGfibrin(ogen) interaction. By immunoassay, HRG-fibrinogen complexes were detected in Zn 2؉ -supplemented human plasma, a finding consistent with a high affinity interaction. Fibrinogen is the soluble precursor of fibrin, a critical component of blood clots that endows them with strength and elasticity. Fibrinogen is a glycoprotein composed of three pairs of polypeptide chains, termed A␣, B␤, and ␥, that are connected by disulfide bonds (1). Approximately 10 -15% of circulating fibrinogen has a variant ␥-chain termed the ␥Ј-chain, which results from differential processing of the ␥ A -chain mRNA transcript (2-4). The ␥Ј-chain is distinguished from the ␥ A -chain by the presence of an acidic 20-residue extension at its COOH terminus (2, 5).Thrombin catalyzes the conversion of fibrinogen to insoluble fibrin, and during this process some thrombin remains bound to the fibrin network (6). Exosites 1 and 2 are two regulatory domains that flank the active site of thrombin and mediate its binding to fibrin (7,8). Exosite 1 of thrombin interacts with the central E-domain of fibrin, whereas exosite 2 binds only to the COOH terminus of the ␥Ј-chain. Consequently, thrombin binds ␥ A /␥ A -fibrin in a univalent fashion with a K d value of 2-4 M. In contrast, both exosites are engaged when thrombin binds to ␥ A /␥Ј-fibrin, resulting in a higher affinity interaction (K d value of 0.08 -0.18 M) (5, 9). Fibrin-bound thrombin remains active, and the protease is protected from inhibition by fluid-phase inhibitors, such as antithrombin and heparin cofactor II (6). Because of its bivalent interaction with ␥ A /␥Ј-fibrin, thrombin bound to ␥ A /␥Ј-fibrin is more protected from inhibition by fluid-phase inhibitors than thrombin bound to ␥ A /␥ Afibrin (10).Like thrombin, histidine-rich glycoprotein (HRG) 3 binds to fibrinogen and is incorporated into fibrin clots (11). Although the plasma concentration of HRG ranges from 1.6 to 2 M, the concentration in platelet-rich thrombi may be higher because HRG is stored in the alpha granules of platelets and is released when platelets are activated (12, 13). A 75-kDa glycoprotein, HRG, is composed of two NH 2 -terminal cystatin-like domains, a central histidine-rich region (HRR) flanked by two prolinerich regions, and a COOH-terminal domain (14). In addition to fibrinogen, HRG also binds plasminogen, heparan sulfate, and divalent cations, such as Zn 2ϩ (12,15,16). Therefore, HRG is hypothesized to be an important accessory or adapter protein that brings different ligands together under specific conditions (14).HRG-deficient mice exhibit a shorter prothrombin time and accelerat...

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Section: Discussionmentioning

confidence: 97%

Section: Histidine-rich Glycoprotein (Hrg) Is An Abundant Protein Thamentioning

confidence: 99%

Histidine-rich Glycoprotein Binds Fibrin(ogen) with High Affinity and Competes with Thrombin for Binding to the γ′-Chain

Stafford

Leslie

et al. 2011

Journal of Biological Chemistry

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“…The studies on the copper(II) complexes of the peptide fragments of prion protein and related substances revealed that the internal histidyl residues can also be anchoring sites for copper(II) or nickel(II) binding [5]. Moreover, the formation of polynuclear copper(II) and/or nickel(II) complexes was observed with various multihistidine peptides [8][9][10][11]. Peptide fragments of prion protein and amyloid-β peptides provided the most evident examples for the binding of more than one copper(II) and nickel(II) ions in these complexes [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Binary and ternary mixed metal complexes of terminally free peptides containing two different histidyl binding sites

Grenács

Kaluha

Kállay

et al. 2013

Journal of Inorganic Biochemistry

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“…Such metal binding sites are obviously difficult to mimic by small peptides. However, a number of proteins possess relatively short histidine-rich sequences with strong metal binding ability, which substantially contributes to the function of the given macromolecule [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Beside the well known human serum albumin (HSA) [1], probably the prion proteins (PrP) [2] are the most studied examples of such sequences.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, a number of studies are reported in the literature dealing with short in-chain sequences as putative metal binding sites of e.g. amyloid precursor protein [14], the repeat sequences of Cap43 [15] and histidine-rich (glyco)proteins [16], the histon H2A protein [17] or the metal-transport protein IRT1 [18]. In spite of the limited analogy between such peptides and the native proteins, in the absence of structural information such studies are of great values, since even the identification of putative metal binding sites may improve our knowledge on the functioning of the given proteins.…”

Section: Introductionmentioning

confidence: 99%

A minimalist chemical model of matrix metalloproteinases — Can small peptides mimic the more rigid metal binding sites of proteins?

Árus¹,

Nagy²,

Dancs³

et al. 2013

Journal of Inorganic Biochemistry

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In order to develop a minimalist chemical model of matrix metalloproteinases (MMPs), we Around pH 6-7 the peptide, similarly to MMPs, offers {3N im } coordinated binding site for both zinc(II) and copper(II). In the case of copper(II), the formation of amide coordinated species at higher pH ceased the analogy with the copper(II) containing MMP variant. On the other hand, the zinc(II)-peptide system mimics some basic features of the MMP active sites: the main species around pH 7 (ZnH 2 L) possesses {3N im ,H 2 O} coordination environment, the deprotonation of the zinc-bound water takes place near to the physiological pH, it forms relatively stable ternary complexes with hydroxamic acids, and the species ZnH 2 L(OH) and ZnH 2 L(OH) 2 have notable hydrolytic activity between pH 7-9.

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Probing the Cu2+ and Zn2+ binding affinity of histidine-rich glycoprotein

Cited by 35 publications

References 61 publications

Histidine-rich Glycoprotein Binds Fibrin(ogen) with High Affinity and Competes with Thrombin for Binding to the γ′-Chain

Histidine-rich Glycoprotein Binds Fibrin(ogen) with High Affinity and Competes with Thrombin for Binding to the γ′-Chain

Binary and ternary mixed metal complexes of terminally free peptides containing two different histidyl binding sites

A minimalist chemical model of matrix metalloproteinases — Can small peptides mimic the more rigid metal binding sites of proteins?

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