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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, H. LU orcid ; Jahnen-Dechent, W. ; Alla, S. A. ; Hock, J. ; Bouma, B. N. and Muller-Esterl, W. (1993) In Journal of Biological Chemistry 268(19). p.14527-14535
Abstract

Prekallikrein, a glycoprotein involved in contact phase activation, circulates in plasma in the form of a binary complex with high molecular weight kininogen (H-kininogen). The binding to H-kininogen is mediated by the prekallikrein heavy chain consisting of four repetitive domains, A1-A4. To define more precisely the region(s) involved in kininogen binding, we have employed an affinity cross-linking strategy with a synthetic peptide of 31 residues which mimics the prekallikrein binding site of H-kininogen. Cross- linking of the radiolabeled peptide to (pre)kallikrein revealed a binding segment in the NH
2-terminal portion of the prekallikrein heavy chain; another binding segment was located in the... (More)

Prekallikrein, a glycoprotein involved in contact phase activation, circulates in plasma in the form of a binary complex with high molecular weight kininogen (H-kininogen). The binding to H-kininogen is mediated by the prekallikrein heavy chain consisting of four repetitive domains, A1-A4. To define more precisely the region(s) involved in kininogen binding, we have employed an affinity cross-linking strategy with a synthetic peptide of 31 residues which mimics the prekallikrein binding site of H-kininogen. Cross- linking of the radiolabeled peptide to (pre)kallikrein revealed a binding segment in the NH
2-terminal portion of the prekallikrein heavy chain; another binding segment was located in the COOH-terminal part of the heavy chain. The latter binding segment is harbored by a previously identified fragment of the kallikrein heavy chain involved in H-kininogen binding (Page, J. D., and Colman, R. W. (1991) J. Biol. Chem. 266, 8143-8148). Chemical cleavage of the heavy chain cross-linked with the radiolabeled peptide mapped the NH
2-terminal binding segment to 60 residues (positions 53-112) of A1. Synthesis of a peptide (positions 56-86) and development of specific antibodies to this peptide narrowed down the kininogen binding segment to 31 residues of the center portion of A1. This NH
2-terminal segment is equivalent to a kininogen binding site previously identified in factor XI (Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1992) J. Biol. Chem. 267, 4247-4252). We conclude that prekallikrein exposes at least two segments on its heavy chain portion which form a continuous surface thereby facilitating the intimate binding of the zymogen to its nonenzymatic cofactor, H- kininogen.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
268
issue
19
pages
14527 - 14535
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • scopus:0027155081
  • pmid:7686159
ISSN
0021-9258
language
English
LU publication?
no
id
a255070d-7e58-49e9-8192-f48de3691c59
alternative location
http://www.jbc.org/content/268/19/14527.full.pdf+html
date added to LUP
2019-12-10 20:21:16
date last changed
2024-01-16 18:24:28
@article{a255070d-7e58-49e9-8192-f48de3691c59,
  abstract     = {{<p>Prekallikrein, a glycoprotein involved in contact phase activation, circulates in plasma in the form of a binary complex with high molecular weight kininogen (H-kininogen). The binding to H-kininogen is mediated by the prekallikrein heavy chain consisting of four repetitive domains, A1-A4. To define more precisely the region(s) involved in kininogen binding, we have employed an affinity cross-linking strategy with a synthetic peptide of 31 residues which mimics the prekallikrein binding site of H-kininogen. Cross- linking of the radiolabeled peptide to (pre)kallikrein revealed a binding segment in the NH<br>
                        <sub>2</sub>-terminal portion of the prekallikrein heavy chain; another binding segment was located in the COOH-terminal part of the heavy chain. The latter binding segment is harbored by a previously identified fragment of the kallikrein heavy chain involved in H-kininogen binding (Page, J. D., and Colman, R. W. (1991) J. Biol. Chem. 266, 8143-8148). Chemical cleavage of the heavy chain cross-linked with the radiolabeled peptide mapped the NH<br>
                        <sub>2</sub>-terminal binding segment to 60 residues (positions 53-112) of A1. Synthesis of a peptide (positions 56-86) and development of specific antibodies to this peptide narrowed down the kininogen binding segment to 31 residues of the center portion of A1. This NH<br>
                        <sub>2</sub>-terminal segment is equivalent to a kininogen binding site previously identified in factor XI (Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1992) J. Biol. Chem. 267, 4247-4252). We conclude that prekallikrein exposes at least two segments on its heavy chain portion which form a continuous surface thereby facilitating the intimate binding of the zymogen to its nonenzymatic cofactor, H- kininogen.</p>}},
  author       = {{Herwald, H. and Jahnen-Dechent, W. and Alla, S. A. and Hock, J. and Bouma, B. N. and Muller-Esterl, W.}},
  issn         = {{0021-9258}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{19}},
  pages        = {{14527--14535}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{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}},
  url          = {{http://www.jbc.org/content/268/19/14527.full.pdf+html}},
  volume       = {{268}},
  year         = {{1993}},
}