Mapping of the high molecular weight kininogen binding site of prekallikrein. Evidence for a discontinuous epitope formed by distinct segments of the prekallikrein heavy chain

Herwald, Heiko; Jahnen‐Dechent, Willi; Alla, Said Abd; Hock, J; Bouma, Bonno N.; Müller‐Esterl, Werner

doi:10.1016/s0021-9258(19)85270-5

Cited by 25 publications

(3 citation statements)

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“…HK31 has been extensively studied (Tait & Fujikawa, 1986, 1987 and has been shown to wholly encompass the prekallikrein binding domain within kininogen. PK56 and PK266 were shown previously to incorporate portions of the kininogen binding domain within kallikrein (Page & Colman, 1991;Herwald et al, 1993;Page et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

“…PK, a single-chain plasma glycoprotein, contains four homologous, unique 90-residue repeat "apple" domains (Chung et al, 1986). The binding site for HK within PK has been mapped to two discontinuous segments of the native protein (Herwald et al, 1993;Page & Colman, 1991;Page et al, 1994), and synthetic peptides encompassing the PK56 of the apple 1 domain and PK266 of the apple 4 domain bind to HK31 with micromolar affinities (Page et al, 1994).…”

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confidence: 99%

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Direct Evidence for Multifacial Contacts between High Molecular Weight Kininogen and Plasma Prekallikrein

Lin¹,

Shenoy²,

Harris³

et al. 1996

Biochemistry

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HK31 (S565-K595) has previously been shown to encompass the binding domain for plasma prekallikrein (PK) within domain 6 of high molecular weight kininogen (HK). The complementary binding domain for HK within PK is mapped to PK56 (F56-G86), in the apple 1 domain, and to PK266 (K266-C295), in the apple 4 domain. Isothermal titration calorimetry was used to directly monitor binding among HK31, PK56, and PK266. Either PK peptide binds to HK31 in 1:1 stoichiometry, regardless of whether a binary complex is first formed between PK266 and HK31 or between PK56 and HK31. Binding of the alternate PK peptide into a ternary complex is facilitated nearly 2-fold. The ternary complex consists of 1:1:1 HK31:PK56:PK266. Furthermore, binary and ternary complex formation is entropically driven and thermodynamically favored, suggesting that the conformational changes accompany binding. Fluorescence emission spectroscopy revealed that binding of PK56 caused a limited decrease in intrinsic tryptophan fluorescence emission intensity of HK31 while binding of PK266 to HK31 or the complex of HK31/PK56 had no such effect. We conclude that the two PK peptides bind to the HK peptide at different sites. The binding between HK and PK is likely due to conformational changes which serve to juxtapose the PK binding domain within HK with the HK binding site involving two spatial proximity segments.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Direct Evidence for Multifacial Contacts between High Molecular Weight Kininogen and Plasma Prekallikrein

Lin¹,

Shenoy²,

Harris³

et al. 1996

Biochemistry

View full text Add to dashboard Cite

show abstract

“…The mature polypeptide of HK is 626 amino acids in length with 6 domains (D1-D6); notably, D3 interacts with platelets, D4 harbors the bradykinin peptide, and D5 contains a histidine-rich region that binds to cell surfaces [19] (Figure 1B). The C-terminal D6 domain interacts with PK and is important for determining the selectivity of HK over low-molecular weight kininogen, which lacks D6 [8,[19][20][21]. The cofactor function of HK is also thought to localize PK and FXI to the correct activated cell membrane.…”

mentioning

confidence: 99%