Site-specific functional roles of the Factor X activation peptide in the intrinsic tenase-mediated Factor X activation.
Factor X
activation peptide
enzyme kinetics
intrinsic tenase
site-directed mutagenesis
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
21
01
2022
received:
10
11
2021
accepted:
12
02
2022
pubmed:
20
2
2022
medline:
30
6
2022
entrez:
19
2
2022
Statut:
ppublish
Résumé
The conversion of zymogen Factor X (FX) to an active protease involves the removal of a 52-residue long activation peptide (AP). Through site-directed mutagenesis, we investigate the role of the AP and demonstrate that the high abundance of proline residues is important for efficient proteolysis of FX. Moreover, we identify an essential interaction site for Factor IXa (FIXa) between residues 22 and 30 (AP numbering) and find that the residues between 31 and 41 may provide an important interaction site for the intrinsic tenase complex, composed of Factor IXa (FIXa) and Factor VIIIa (FVIIIa). Finally, we suggest that the carbohydrate chain at Asn-39 restricts the activator specificity, as elimination of this glycosylation site increases the activation rate for activation by FIXa and FXa.
Identifiants
pubmed: 35181908
doi: 10.1002/1873-3468.14321
doi:
Substances chimiques
Neoplasm Proteins
0
Peptides
0
Factor X
9001-29-0
Factor IXa
EC 3.4.21.22
Cysteine Endopeptidases
EC 3.4.22.-
cancer procoagulant
EC 3.4.22.26
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1567-1575Informations de copyright
© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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