Functional sites of bovine high molecular weight kininogen as a cofactor in kaolin-mediated activation of factor XII (Hageman factor)

Sugo, Teruko; Ikari, Nobuhiko; Kato, Harubumi; Iwanaga, Sadaaki; Fujii, Satoshi

doi:10.1021/bi00555a018

Cited by 50 publications

(9 citation statements)

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“…When bovine HK is digested with bovine kallikrein, a polypeptide was removed from the light chain corresponding to the histidine-glycine-rich domain of human HK (Han et al, 1976;Sugo et al, 1980;Ikari et al, 1981), which results in both the loss of coagulant activity and ability of cleaved bovine HK to bind to negatively charged surfaces. In human HK, unlike bovine HK, there is a substitution of Lys at position 402 for Arg that results in failure of human plasma kallikrein, which prefers arginine residues, to cleave the corresponding peptide from human HK.…”

Section: Discussionmentioning

confidence: 99%

“…The light chain of HK contains the procoagulant activity (Mandle et al, 1976), which depends in part on its ability to associate with the zymogens, PK, through residues 556-595 of HK, or FXI, through residues 556-613 (Tait & Fujikawa, 1987). The coagulant activity of HK also depends on the binding of cleaved HK (Sugo et al, 1980) to anionic surfaces. This function is thought to be mediated through its histidineglycine-rich region (residues 407-498).…”

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confidence: 99%

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The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

Dela

Colman

1992

Protein Science

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The histidine-glycine-rich region of the light chain of cleaved high molecular weight kininogen (HK) is thought to be responsible for binding to negatively charged surfaces and initiation of the intrinsic coagulation, fibrinolytic, and kinin-forming systems. However, the specifically required amino acid sequences have not been delineated. An IgG fraction of a monoclonal antibody (MAb) CllCl to the HK light chain was shown to inhibit by 66% the coagulant activity and by 57% the binding of HK to the anionic surface of kaolin at a concentration of 1.5 pM and 27 pM, respectively. Proteolytic fragments of HK were produced by successive digestion with human plasma kallikrein and factor XIa (FXIa). Those polypeptides that bound tightly (Kd = 0.77 nM) to a C11C1 affinity column were eluted at pH 3.0 and purified by membrane filtration. On 15% SDS polyacrylamide electrophoresis, the approximate M, was 7.3 kDa (range 6.2-8.1 kDa). Based on N-terminal sequencing, this polypeptide (I2), which extends from the histidine residue 459 to a lysine at position 505, 509, 51 1, 512, 515, or 520, inhibits by 50% the coagulant activity expressed by HK at a concentration of 22 pM. The synthetic peptide HGLGHGH representing the N-terminal of the l2 fragment was synthesized, tested, and found at 4 mM to inhibit the procoagulant activity of HK 50%. A synthetic heptadecapeptide, HGLGHGHEQQHGLGHGH (residues 459-475) included within the l2 fragment, and with the ability to bind zinc, inhibited 50% of the HK coagulant activity at a concentration of 325 pM in the absence and presence of added Zn2+ (30 pM). The specific binding of 12'I-HK to a negatively charged surface (kaolin) was inhibited 50% by unlabeled HK (5 pM). HGLGHGH, at a concentration of 7.0 mM, inhibited the binding to kaolin by 50%. The heptadecapeptide inhibited the specific binding of I2'I-HK to kaolin by 50%, at a concentration of 2.3 mM, in the absence of Zn2+.In contrast, when Zn2+ was added, the concentration to achieve 50% inhibition decreased to 630 pM, indicating that Zn2+ was required to attain a favorable conformation for binding. Moreover, the I, fragment was found to inhibit 50% of the I2'I-HK binding to kaolin at a concentration of 380 pM. These results suggest that residues contained within the 1, fragment, notably HGLGHGHEQQHGLGHGH, serves as a primary structural feature for binding to a negatively charged surface.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

Dela

Colman

1992

Protein Science

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“…The alkylated heavy chain had no procoagulant activity, whereas the light chain possessed the entire procoagulant activ ity of the parent molecule. 30,61,66 The heavy chain shares antigenic determinants with the heavy chain of low Mr kininogen and these chains are highly homologous in amino acid sequences. Recently, the complete amino acid sequences of the light chains of human high and low Mr kininogen were re ported.…”

Section: Structure-function Relationship Of High Molecular Weight Kinmentioning

confidence: 99%

“…Moreover, this portion of the carboxy terminal region of the high Mr kininogen molecule has been shown to be essential for the contact activation cofactor activity. 26,27,61 It may be speculated that this highly positively charged region of the molecule is responsible for the binding of the molecule to negatively charged surfaces.…”

Section: Structure-function Relationship Of High Molecular Weight Kinmentioning

confidence: 99%

Role of High Molecular Weight Kininogen in Contact Activation

Iwaarden¹,

Bouma²

1987

Semin Thromb Hemost

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“…The 56 kDa light chain of the HK (LC 1) is further cleaved to a 45 kDa light chain (LC 2) by kallikrein. The heavy chain contains cysteine protease inhibitory domains, while the LC of HK contains the anionic surface binding domain, the region binding the zymogens, PK and FXI (8)(9)(10) and a heparin binding site. The HK LC binds to surfaces and the attached PK is thereby Correspondence to: Dr. Satya P. Kunapuli, Thrombosis Research Center, Temple lJniversity School of Medicine, 3400 North Broad Street, Philadelphia, PA I9I40, USA positioned for cleavage, which results in the exposure of the active site of kallikrein (11).…”

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confidence: 99%

Bacterial Expression of Biologically Active High Molecular Weight Kininogen Light Chain

1992

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SummaryHuman high molecular weight kininogen (HK), a single chain plasma glycoprotein, serves as a cofactor in the contact system of blood coagulation. After cleavage by human plasma kallikrein, the nonapeptide bradykinin is released. The HK light chain (LC) contains coagulant activity, which requires both the ability to bind the contact system zymogens, prekallikrein and factor XI, and the ability to interact with negatively charged surfaces. Since bacterial expression might not be successful if carbohydrate was required for activity, we evaluated that possibility by incubating plasma HK with endoglycosydase F. Although the procedure removed detectable N-linked carbohydrate, no change in specific activity occurred. We then developed a bacterial expression system to produce recombinant HK LC. The cDNA coding for the HK LC was prepared by polymerase chain reaction (PCR), digested with restriction enzymes EcoRI and PstI, and introduced into the bacterial expression vector pKK223-3. E. coli harboring this recombinant plasmid (pSKl) expressed HK LC upon induction with isopropylthio-galactoside (IPTG). The recombinant protein (27 kDa), when transferred onto a PVDF membrane, was recognized by monospecific polyclonal anti-HK LC-antibodies. The recombinant HK LC was purified by heparin agarose affinity chromatography to homogeneity and found to have a specific activity of 28 coagulant units per mg protein, similar to the specific activity of the LC derived by proteolytic digestion of human plasma HK. We conclude: 1) The HK LC synthesized in bacteria is biologically active, and 2) the 40% carbohydrate content of the HK LC is not required for its cofactor activity.

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Functional sites of bovine high molecular weight kininogen as a cofactor in kaolin-mediated activation of factor XII (Hageman factor)

Cited by 50 publications

References 30 publications

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

Role of High Molecular Weight Kininogen in Contact Activation

Bacterial Expression of Biologically Active High Molecular Weight Kininogen Light Chain

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