Polymerization defect of fibrinogen Baltimore III due to a gamma Asn308----Ile mutation.
Fibrinogen Baltimore III, a congenital abnormal fibrinogen with impaired fibrin monomer polymerization, displays a normal gamma-chain and a gamma-variant that has an apparently lower relative molecular weight (mol wt) than normal on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Reverse phase high-performance liquid chromatography (HPLC) analysis of the lysyl endopeptidase digest of the purified gamma-chains of fibrinogen Baltimore III revealed the presence of a peptide that is not found in the digest of the normal fibrinogen gamma-chain. Amino acid sequence analysis of this peptide indicated that the gamma-chain residue 308, asparagine, is replaced by isoleucine. Concanavalin A bound both normal and variant gamma-chains of fibrinogen Baltimore III, indicating that the carbohydrate moiety is not altered and is not responsible for the increase in electrophoretic mobility of the Baltimore III gamma-chain. This study suggests that the integrity of gamma Asn308 is critical for fibrin monomer polymerization, since alteration to either a basic (fibrinogen Kyoto I, Asn----Lys) or hydrophobic (Asn----Ile) residue results in significantly delayed polymerization of fibrinogen to fibrin.
Bantia
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Bell
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Dang
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D001216:Asparagine / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003208:Concanavalin A / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005338:Fibrin Fibrinogen Degradation Products; D015241:Fibrinogens, Abnormal / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007532:Isoleucine / Q000032:analysis* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011108:Polymers; D012697:Serine Endopeptidases / Q000494:pharmacology
D000596:Amino Acids; D005338:Fibrin Fibrinogen Degradation Products; D015241:Fibrinogens, Abnormal; D011108:Polymers; C011468:fibrinmonomer; C057431:fibrinogen Baltimore III; D007532:Isoleucine; D003208:Concanavalin A; D001216:Asparagine; D012697:Serine Endopeptidases; C036813:lysyl endopeptidase