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Novel subunit in C4b-binding protein required for protein S binding

Hillarp, A LU and Dahlbäck, B LU (1988) In The Journal of biological chemistry 263(25). p.64-12759
Abstract

C4b-binding protein (C4BP) is a multimeric protein with regulatory functions in the complement system. It also interacts with vitamin K-dependent protein S, which is involved in the regulation of the coagulation system. It has been demonstrated that C4BP consists of seven disulfide-linked, identical 70-kDa subunits, which are arranged to give the molecule a spider-like structure. We now have evidence for the presence of a new subunit in C4BP. On sodium dodecyl sulfate-poly-acrylamide gel electrophoresis it appears as a weakly stainable band with a molecular weight of approximately 45,000. The subunit was isolated by gel filtration in 6 M guanidine hydrochloride of reduced and carboxymethylated C4BP. Its amino-terminal sequence is... (More)

C4b-binding protein (C4BP) is a multimeric protein with regulatory functions in the complement system. It also interacts with vitamin K-dependent protein S, which is involved in the regulation of the coagulation system. It has been demonstrated that C4BP consists of seven disulfide-linked, identical 70-kDa subunits, which are arranged to give the molecule a spider-like structure. We now have evidence for the presence of a new subunit in C4BP. On sodium dodecyl sulfate-poly-acrylamide gel electrophoresis it appears as a weakly stainable band with a molecular weight of approximately 45,000. The subunit was isolated by gel filtration in 6 M guanidine hydrochloride of reduced and carboxymethylated C4BP. Its amino-terminal sequence is distinct from previously known protein sequences. The stoichiometry of 45- to 70-kDa subunits was estimated to be 1:9, indicating the presence of one 45-kDa subunit per C4BP molecule. The new subunit was demonstrated to be a disulfide-linked component of the central core of C4BP. It was sensitive to proteolysis by chymotrypsin, and when cleaved the protein S binding ability of C4BP was lost. With protein S bound to C4BP, the 45-kDa subunit was protected from degradation by chymotrypsin, and the protein S binding site remained intact. These data suggest that the new subunit is directly involved in protein S binding.

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subject
keywords
Amino Acid Sequence, Binding Sites, Carrier Proteins/isolation & purification, Chromatography, Gel, Chymotrypsin/metabolism, Complement C4, Complement Inactivator Proteins, Disulfides/metabolism, Electrophoresis, Polyacrylamide Gel, Glycoproteins/metabolism, Guanidine, Guanidines, Humans, Immunoassay, Macromolecular Substances, Molecular Sequence Data, Molecular Weight, Peptide Fragments/isolation & purification, Protein S, Receptors, Complement
in
The Journal of biological chemistry
volume
263
issue
25
pages
64 - 12759
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • scopus:0024245613
  • pmid:2970465
ISSN
0021-9258
DOI
10.1016/S0021-9258(18)37818-9
language
English
LU publication?
yes
id
25ab1f67-d060-4f00-ac29-b9dbef273a49
date added to LUP
2022-08-29 10:37:02
date last changed
2024-02-18 07:26:26
@article{25ab1f67-d060-4f00-ac29-b9dbef273a49,
  abstract     = {{<p>C4b-binding protein (C4BP) is a multimeric protein with regulatory functions in the complement system. It also interacts with vitamin K-dependent protein S, which is involved in the regulation of the coagulation system. It has been demonstrated that C4BP consists of seven disulfide-linked, identical 70-kDa subunits, which are arranged to give the molecule a spider-like structure. We now have evidence for the presence of a new subunit in C4BP. On sodium dodecyl sulfate-poly-acrylamide gel electrophoresis it appears as a weakly stainable band with a molecular weight of approximately 45,000. The subunit was isolated by gel filtration in 6 M guanidine hydrochloride of reduced and carboxymethylated C4BP. Its amino-terminal sequence is distinct from previously known protein sequences. The stoichiometry of 45- to 70-kDa subunits was estimated to be 1:9, indicating the presence of one 45-kDa subunit per C4BP molecule. The new subunit was demonstrated to be a disulfide-linked component of the central core of C4BP. It was sensitive to proteolysis by chymotrypsin, and when cleaved the protein S binding ability of C4BP was lost. With protein S bound to C4BP, the 45-kDa subunit was protected from degradation by chymotrypsin, and the protein S binding site remained intact. These data suggest that the new subunit is directly involved in protein S binding.</p>}},
  author       = {{Hillarp, A and Dahlbäck, B}},
  issn         = {{0021-9258}},
  keywords     = {{Amino Acid Sequence; Binding Sites; Carrier Proteins/isolation & purification; Chromatography, Gel; Chymotrypsin/metabolism; Complement C4; Complement Inactivator Proteins; Disulfides/metabolism; Electrophoresis, Polyacrylamide Gel; Glycoproteins/metabolism; Guanidine; Guanidines; Humans; Immunoassay; Macromolecular Substances; Molecular Sequence Data; Molecular Weight; Peptide Fragments/isolation & purification; Protein S; Receptors, Complement}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{25}},
  pages        = {{64--12759}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{The Journal of biological chemistry}},
  title        = {{Novel subunit in C4b-binding protein required for protein S binding}},
  url          = {{http://dx.doi.org/10.1016/S0021-9258(18)37818-9}},
  doi          = {{10.1016/S0021-9258(18)37818-9}},
  volume       = {{263}},
  year         = {{1988}},
}