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
(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
(Less)
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.
- author
- Herwald, H. LU ; Jahnen-Dechent, W. ; Alla, S. A. ; Hock, J. ; Bouma, B. N. and Muller-Esterl, W.
- publishing date
- 1993-07-05
- 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}}, }