Fibrinogens Kawaguchi and Osaka: an amino acid substitution of A alpha arginine-16 to cysteine which forms an extra interchain disulfide bridge between the two A alpha chains.
Structural analyses of fibrinogens from patients with congenital dysfibrinogenemia, designated as fibrinogens Kawaguchi and Osaka, have been performed to identify the difference responsible for the lack of fibrinopeptide A release. For the structural studies, a new strategy was employed. Amino acid sequence analysis of one of the lysyl endopeptidase-peptides isolated from the abnormal fibrinogens indicated that in both fibrinogens, arginine-16 of the A alpha chain had been replaced by cysteine. To characterize the chemical nature of the sulfhydryl group of cysteine-16, a tryptic peptide containing cysteine-16 of the A alpha chain was prepared from intact fibrinogen Kawaguchi. The amino acid composition and the molecular weight determination of this aberrant peptide revealed that it was a dimeric NH2-terminal peptide corresponding to residues 1-19 derived from the abnormal A alpha chain. These results indicate that the half-cystine at position 16 in the abnormal A alpha chain forms an intramolecular disulfide bridge with the same residue in the other abnormal A alpha chain and that fibrinogen Kawaguchi is a homo dimer composed of two identical abnormal halves.
Miyata
T
T
Department of Biology, Faculty of Science, Kyushu University, Fukuoka.
Terukina
S
S
Matsuda
M
M
Kasamatsu
A
A
Takeda
Y
Y
Murakami
T
T
Iwanaga
S
S
D000595:Amino Acid Sequence; D001120:Arginine; D001778:Blood Coagulation Disorders / Q000097:blood*; D003545:Cysteine; D004220:Disulfides; D005340:Fibrinogen / Q000235:genetics* / Q000302:isolation & purification; D015241:Fibrinogens, Abnormal; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight
D004220:Disulfides; D015241:Fibrinogens, Abnormal; D046911:Macromolecular Substances; C045162:fibrinogen Kawaguchi; D005340:Fibrinogen; D001120:Arginine; D003545:Cysteine