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Titolo:
NATURALLY-OCCURRING ARG(-1) TO HIS MUTATION IN HUMAN PROTEIN-C LEADS TO ABERRANT PROPEPTIDE PROCESSING AND SECRETION OF DYSFUNCTIONAL PROTEIN-C
Autore:
LIND B; JOHNSEN AH; THORSEN S;
Indirizzi:
RIGSHOSP,DEPT CLIN BIOCHEM KB 3 01 1,SECT HEMOSTASIS & THROMBOSIS,BLEGDAMSVEJ 9 DK-2100 COPENHAGEN DENMARK
Titolo Testata:
Blood
fascicolo: 8, volume: 89, anno: 1997,
pagine: 2807 - 2816
SICI:
0006-4971(1997)89:8<2807:NATHMI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-CARBOXYGLUTAMIC ACID; K-DEPENDENT PROTEINS; FACTOR-IX PRECURSOR; MEMBRANE-BINDING; POINT MUTATIONS; GLA-DOMAIN; VENOUS THROMBOSIS; PROTHROMBIN FRAGMENT-1; ANTICOAGULANT ACTIVITY; BLOOD-COAGULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
B. Lind et al., "NATURALLY-OCCURRING ARG(-1) TO HIS MUTATION IN HUMAN PROTEIN-C LEADS TO ABERRANT PROPEPTIDE PROCESSING AND SECRETION OF DYSFUNCTIONAL PROTEIN-C", Blood, 89(8), 1997, pp. 2807-2816

Abstract

The dysfunctional protein C from a thrombophilic patient heterozygotefor a G(1388) to A converting the codon for Arg(-1) to His was purified from plasma and characterized. N-terminal amino acid sequence analysis of the light chain of the protein C demonstrated that the dysfunctional protein C is elongated with one amino acid, namely the mutated His. This finding is compatible with disruption by the mutated His of the original basic propeptidase recognition sequence (Arg(-5)-Ile-Arg-Lys-Arg(-1)), resulting in a shift of the cleavage site to a new position, Lys(-2)-His(-1), which follows an alternative basic amino acid propeptidase recognition sequence (Arg(-5)-Ile-Arg-Lys(-2)). Because the mutation affects the propeptide that directs the gamma-carboxylation converting Glu to Gla residues in the Gla domain, it was investigated whether the mutation impaired this reaction. Gla fragment obtained by cleavage of the dysfunctional protein C light chain with endoproteinaseAsp-N was isolated by reverse-phase highperformance liquid chromatography, methylated, and subjected to N-terminal sequence analysis, The methylation step enabled the positive identification of Gla residues aswell as the determination of the relative amount of Gla and Glu residues at each of the nine gamma-carboxylation sites of the Gla domain, The analysis showed that all nine potential gamma-carboxylation sites of the dysfunctional protein C were normally carboxylated. This result is compatible with the notion that position -1 is not a part of the recognition element for the gamma-carboxylase, In conclusion, evidence is provided showing that the mutation leads to aberrant propeptide processing and secretion of dysfunctional normally carboxylated protein C extended with the mutated His. (C) 1997 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:36:18