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Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4

Standard

Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4. / Herwald, H; Renné, T; Meijers, J C; Chung, D W; Page, J D; Colman, R W; Müller-Esterl, W.

In: J BIOL CHEM, Vol. 271, No. 22, 31.05.1996, p. 13061-7.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Herwald, H, Renné, T, Meijers, JC, Chung, DW, Page, JD, Colman, RW & Müller-Esterl, W 1996, 'Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4', J BIOL CHEM, vol. 271, no. 22, pp. 13061-7.

APA

Herwald, H., Renné, T., Meijers, J. C., Chung, D. W., Page, J. D., Colman, R. W., & Müller-Esterl, W. (1996). Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4. J BIOL CHEM, 271(22), 13061-7.

Vancouver

Herwald H, Renné T, Meijers JC, Chung DW, Page JD, Colman RW et al. Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4. J BIOL CHEM. 1996 May 31;271(22):13061-7.

Bibtex

@article{b4e5993b81ed4c7691c13a66a6b4de0c,
title = "Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4",
abstract = "Prekallikrein, the precursor to the serine proteinase kallikrein, circulates in plasma in an equimolar complex with H-kininogen. The binding to H-kininogen is mediated by the kallikrein heavy chain consisting of four {"}apple{"} domains, A1-A4, which attaches to H-kininogen with high specificity and affinity (KD = 83 nM). At least two distinct portions of the kallikrein heavy chain form this H-kininogen binding site: a proximal segment located in the NH2-terminal fragment of the heavy chain encompassing A1, and distal segment(s) located in COOH-terminal fragment spanning domains A2-A4. The proximal binding segment has been located to amino acid positions 56-86 of A1. To precisely map the distal binding segment, we have identified monoclonal antibodies directed to the COOH-terminal fragment which interfere with the H-kininogen-prekallikrein complex formation. Monoclonal antibody 13G11 binds to recombinant apple domain A4 but not to domain A3 of the prekallikrein heavy chain. Deletion mutagenesis of domain A4 narrowed down the target epitope of 13G11 to the center portion of domain A4, positions 284-331. Direct binding studies of H-kininogen to various domain A4 constructs revealed that the distal H-kininogen binding portion is located on a segment of 48 residues, which overlaps the 13G11 epitope. Hence the tight interaction of H-kininogen and prekallikrein is mediated by at least two separate sequence segments located in domains A1 and A4, respectively, of the prekallikrein heavy chain. The isolated distal binding segment significantly prolongs the partial thromboplastin time of reconstituted Williams plasma thus stressing the critical role of the prekallikrein-H-kininogen complex formation in the initiation of the endogenous blood coagulation cascade.",
keywords = "Animals, Antibodies, Monoclonal, Base Sequence, Binding Sites, Blotting, Western, Cell Line, Cricetinae, Cyanogen Bromide, DNA Primers, Epitopes, Humans, Kininogens, Molecular Sequence Data, Partial Thromboplastin Time, Peptide Mapping, Prekallikrein",
author = "H Herwald and T Renn{\'e} and Meijers, {J C} and Chung, {D W} and Page, {J D} and Colman, {R W} and W M{\"u}ller-Esterl",
year = "1996",
month = may,
day = "31",
language = "English",
volume = "271",
pages = "13061--7",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "22",

}

RIS

TY - JOUR

T1 - Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4

AU - Herwald, H

AU - Renné, T

AU - Meijers, J C

AU - Chung, D W

AU - Page, J D

AU - Colman, R W

AU - Müller-Esterl, W

PY - 1996/5/31

Y1 - 1996/5/31

N2 - Prekallikrein, the precursor to the serine proteinase kallikrein, circulates in plasma in an equimolar complex with H-kininogen. The binding to H-kininogen is mediated by the kallikrein heavy chain consisting of four "apple" domains, A1-A4, which attaches to H-kininogen with high specificity and affinity (KD = 83 nM). At least two distinct portions of the kallikrein heavy chain form this H-kininogen binding site: a proximal segment located in the NH2-terminal fragment of the heavy chain encompassing A1, and distal segment(s) located in COOH-terminal fragment spanning domains A2-A4. The proximal binding segment has been located to amino acid positions 56-86 of A1. To precisely map the distal binding segment, we have identified monoclonal antibodies directed to the COOH-terminal fragment which interfere with the H-kininogen-prekallikrein complex formation. Monoclonal antibody 13G11 binds to recombinant apple domain A4 but not to domain A3 of the prekallikrein heavy chain. Deletion mutagenesis of domain A4 narrowed down the target epitope of 13G11 to the center portion of domain A4, positions 284-331. Direct binding studies of H-kininogen to various domain A4 constructs revealed that the distal H-kininogen binding portion is located on a segment of 48 residues, which overlaps the 13G11 epitope. Hence the tight interaction of H-kininogen and prekallikrein is mediated by at least two separate sequence segments located in domains A1 and A4, respectively, of the prekallikrein heavy chain. The isolated distal binding segment significantly prolongs the partial thromboplastin time of reconstituted Williams plasma thus stressing the critical role of the prekallikrein-H-kininogen complex formation in the initiation of the endogenous blood coagulation cascade.

AB - Prekallikrein, the precursor to the serine proteinase kallikrein, circulates in plasma in an equimolar complex with H-kininogen. The binding to H-kininogen is mediated by the kallikrein heavy chain consisting of four "apple" domains, A1-A4, which attaches to H-kininogen with high specificity and affinity (KD = 83 nM). At least two distinct portions of the kallikrein heavy chain form this H-kininogen binding site: a proximal segment located in the NH2-terminal fragment of the heavy chain encompassing A1, and distal segment(s) located in COOH-terminal fragment spanning domains A2-A4. The proximal binding segment has been located to amino acid positions 56-86 of A1. To precisely map the distal binding segment, we have identified monoclonal antibodies directed to the COOH-terminal fragment which interfere with the H-kininogen-prekallikrein complex formation. Monoclonal antibody 13G11 binds to recombinant apple domain A4 but not to domain A3 of the prekallikrein heavy chain. Deletion mutagenesis of domain A4 narrowed down the target epitope of 13G11 to the center portion of domain A4, positions 284-331. Direct binding studies of H-kininogen to various domain A4 constructs revealed that the distal H-kininogen binding portion is located on a segment of 48 residues, which overlaps the 13G11 epitope. Hence the tight interaction of H-kininogen and prekallikrein is mediated by at least two separate sequence segments located in domains A1 and A4, respectively, of the prekallikrein heavy chain. The isolated distal binding segment significantly prolongs the partial thromboplastin time of reconstituted Williams plasma thus stressing the critical role of the prekallikrein-H-kininogen complex formation in the initiation of the endogenous blood coagulation cascade.

KW - Animals

KW - Antibodies, Monoclonal

KW - Base Sequence

KW - Binding Sites

KW - Blotting, Western

KW - Cell Line

KW - Cricetinae

KW - Cyanogen Bromide

KW - DNA Primers

KW - Epitopes

KW - Humans

KW - Kininogens

KW - Molecular Sequence Data

KW - Partial Thromboplastin Time

KW - Peptide Mapping

KW - Prekallikrein

M3 - SCORING: Journal article

C2 - 8662705

VL - 271

SP - 13061

EP - 13067

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 22

ER -