scholarly journals Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI

2019 ◽  
Vol 17 (5) ◽  
pp. 759-770 ◽  
Author(s):  
Chan Li ◽  
Kayleigh M. Voos ◽  
Monika Pathak ◽  
Gareth Hall ◽  
Keith R. McCrae ◽  
...  
Keyword(s):  
Plasma Kallikrein ◽  
Factor Xi ◽  
Apple Domain

scholarly journals An Inventory of Plasminogen Activators in Human Plasma

1977 ◽  
Author(s):  
C. Kluft
Keyword(s):  
Plasminogen Activators ◽  
Venous Occlusion ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Dextran Sulphate ◽  
Factor Xi ◽  
Dependent Component ◽  
Unidentified Component ◽  
Altered Response ◽  
Activator System

Plasma plasminogen (pro) activators were activated and precipitated completely in a euglobulin fraction by means of dextran sulphate. Total activator activity was measured by adding flufena-mate which rules out the influence of precipitated C1-inactivator on intrinsic activator system(s); extrinsic or vascular activator activity resistant to C1-inactivator was measured separately by adding extra C1-inactivator. In normal morning plasma, a total level of 100 + 15 (n=50) arbitrary blood activator units (BAU)/ml was detected; after 15 min venous occlusion, plasma contained 249 + 27 BAU/ml (n=7). The contribution of extrinsic activator amounted to a few percent in morning plasma and around 120 BAU/ml in occlusion plasma. The measured activator activity in morning plasma originates mainly from the intrinsic system(s) and was subdivided roughly into two equal components, one dependent on factor XII and one apparently independent of factor XII. The latter was found in Hageman trait (52 BAU/ml; n=3) and Fletcher trait plasma (44 BAU/ml; n=2). The factor XI I-dependent component was revealed by the correction of the deficiencies with factor XII (1%) and purified plasma kallikrein (100,000 and 300,000 daltons, 50-75%), respectively. Fitzgerald trait plasma (84 BAU/ml; n=1) did not show an altered response. Activator activity (10-15 BAU/ml plasma) found in partially purified kallikrein preparations of 100,000 as well as 300,000 daltons seems to be a property of the kallikrein. Thus, the total amount of activator activity found in morning plasma is made up by a few percent extrinsic activator, 10-15% kallikrein, 30-40% factor XI I-dependent activator and 40-50% unidentified component(s).

Molecular characterization of in-frame and out-of-frame alternative splicings in coagulation factor XI pre-mRNA

Blood ◽  
2010 ◽  
Vol 115 (10) ◽  
pp. 2065-2072 ◽  
Author(s):  
Rosanna Asselta ◽  
Valeria Rimoldi ◽  
Ilaria Guella ◽  
Giulia Soldà ◽  
Raimondo De Cristofaro ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Mammalian Cells ◽  
Ex Vivo ◽  
Coagulation Factor ◽  
Factor Xi ◽  
Mrna Isoforms ◽  
Central Process ◽  
Serine Protease Domain ◽  
Apple Domain ◽  
The One

Abstract Alternative splicing of pre-mRNAs is a central process to the generation of proteome complexity. However, many alternative mRNA isoforms carry premature termination codons (PTCs) rendering them possible targets for the nonsense-mediated mRNA decay (NMD) pathway. The F11 gene consists of 15 exons spanning approximately 23 kb on chromosome 4q35 and codes for coagulation factor XI (FXI), a 160-kDa dimeric zymogen composed of 4 apple domains and a serine protease domain. Here, we characterized the F11 splicing pattern in human liver and platelets identifying multiple in-frame and out-of-frame splicing events. Inhibition of NMD resulted in the up-regulation of all unproductively spliced F11 transcripts, thus providing evidence that these PTC-containing mRNAs are under the control of NMD. Among in-frame alternatively spliced transcripts, the one skipping exons 6 and 7 would lead to the synthesis of a FXI protein lacking 1 apple domain (FXI-Δ6/7). Ex vivo expression in mammalian cells demonstrated that FXI-Δ6/7 is mostly retained intracellularly, and secreted only in low amounts. Traces of this FXI isoform were detectable in human plasma. Our results suggest that the coupling of alternative splicing and NMD may play a role in regulating F11 expression, and point to the existence of a novel FXI isoform.

scholarly journals Six point mutations that cause factor XI deficiency

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1509-1516 ◽  
Author(s):  
RE Pugh ◽  
JH McVey ◽  
EG Tuddenham ◽  
JF Hancock
Keyword(s):  
Amino Acid ◽  
Point Mutations ◽  
Bleeding Disorder ◽  
The Other ◽  
Amino Acid Substitutions ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Amino Terminal ◽  
Apple Domain

We have identified six novel types of mutation that cause factor XI deficiency, an inherited bleeding disorder. Two are point mutations that interfere with the normal splicing of exons in the mRNA and four are point mutations that result in amino acid substitutions. One of these amino acid substitutions (Asp 16-->His) is near the amino terminal end of the protein. The other three amino acid substitutions (Leu 302-->Pro, Thr 304-->Ile, and Glu 323-->Lys) are in the fourth apple domain, a region that mediates dimerization of identical subunits of factor XI. All four amino acid substitutions cause a reduction in the amount of factor XI secreted from cells grown in vitro.

Contact phase of blood coagulation is not activated in edema of high altitude

1989 ◽  
Vol 67 (4) ◽  
pp. 1336-1340 ◽  
Author(s):  
P. Bartsch ◽  
B. Lammle ◽  
I. Huber ◽  
A. Haeberli ◽  
P. Vock ◽  
...  
Keyword(s):  
High Altitude ◽  
Blood Coagulation ◽  
Proteolytic Cleavage ◽  
Contact System ◽  
Acute Exposure ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Contact Activation ◽  
Factor Xi ◽  
Contact Phase

To examine whether bradykinin generated by the activation of the contact phase of blood coagulation is involved in the pathogenesis of edema occurring after acute exposure to high altitude, 15 mountaineers were examined at 490 m and 1, 3, and 5 days after arrival at 4,559 m. The clotting activity levels of factor XII, factor XI, plasma prekallikrein, and high-molecular-weight kininogen (HMWK) were measured, and plasma kallikrein-induced proteolytic cleavage of HMWK was assessed by ligand blotting by use of radiolabeled factor XI. After an ascent on foot from 1,170 to 4,559 m in 3 days, three subjects developed high-altitude pulmonary edema, and four subjects presented facial edema. There was no evidence for activation of the contact system in any subject as demonstrated by the lack of proteolytic cleavage of HMWK at high altitude. The absence of contact system activation was further supported by stable plasma levels of the individual factors of contact activation. Therefore, we conclude that bradykinin generated by plasma kallikrein-induced cleavage of HMWK is not involved in the pathogenesis of edema due to acute exposure to high altitude.

Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

1998 ◽  
Vol 80 (08) ◽  
pp. 233-238 ◽  
Author(s):  
K. A. Mitropoulos ◽  
M. N. Nanjee ◽  
D. J. Howarth ◽  
J. C. Martin ◽  
M. P. Esnouf ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Positive Association ◽  
Factor Ix ◽  
Factor Vii ◽  
Unesterified Fatty Acid ◽  
Factor Xii ◽  
Factor X ◽  
Factor Xi ◽  
Activated Factor Vii ◽  
Normal Mean

SummaryAbetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyce-ride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 μmol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients’ mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

Cold Promoted Activation of Factor VII

1972 ◽  
Vol 28 (02) ◽  
pp. 169-181 ◽  
Author(s):  
H Gjønnæss
Keyword(s):  
Low Temperature ◽  
Oral Contraceptives ◽  
Fold Increase ◽  
Factor Vii ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Overnight Incubation ◽  
Esterolytic Activity

SummaryThe activating principle (CPA) of the factor VII activation seen in plasmas of women taking oral contraceptives after overnight incubation of the plasmas at 0° C was investigated. The reaction was dependent on low temperature, and factor XII was indispensable. Concomitant with the activation of factor VII a 10–30 fold increase in TAME esterolytic activity was observed together with a near 100 per cent drop in plasma kininogen concentration. The results indicated that the activation of factor VII is linked to activation of the kallikrein system, and that the activator may be plasma kallikrein.

Cold Promoted Activation of Factor VII VI. Effect of Inhibitors

1973 ◽  
Vol 29 (03) ◽  
pp. 633-643
Author(s):  
H Gjønnæss
Keyword(s):  
Soya Bean ◽  
Factor Vii ◽  
Plasma Kallikrein ◽  
Contact Activation ◽  
Activation Reaction ◽  
Hexadimethrine Bromide ◽  
Bean Trypsin Inhibitor ◽  
Plasma Arginine ◽  
Kallikrein Activity ◽  
Effect Of Inhibitors

SummaryThe cold promoted activation of factor VII occurs in parallel with an activation of a plasma arginine esterase, and, on inhibition of the cold activation of factor VII, the esterase activation also decreased. The inhibitor pattern supported our theory that the arginine esterase that is activated in the cold activation of factor VII is plasma kallikrein.The cold activation of factor VII was completely inhibited with soya bean trypsin inhibitor in doses that did not interfere with the contact activation. On the other hand, inhibition of the contact activation with hexadimethrine bromide did not interfere with the cold activation of factor VII except when this was kaolin induced. Contact and cold activation therefore appear to represent two different pathways for the activation of factor VII. The cold activation reaction is probably mediated by the activation of plasma prekallikrein, and inhibition of the plasma kallikrein activity correlates with the inhibition of the cold promoted activation of factor VII.

Functional Characterization of a Variant Factor XII (F XII Locarno) in a Cross Reacting Material Positive F XII Deficient Plasma

1992 ◽  
Vol 67 (02) ◽  
pp. 219-225 ◽  
Author(s):  
Walter A Wuillemin ◽  
Miha Furlan ◽  
Hans Stricker ◽  
Bernhard Lämmle
Keyword(s):  
Dextran Sulfate ◽  
Functional Characterization ◽  
Healthy Woman ◽  
Chain Molecule ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Single Chain ◽  
Sulfate Adsorption ◽  
Prolonged Incubation ◽  
Functional Studies

SummaryThe plasma of a healthy woman was found to contain half normal factor XII (FXII) antigen level (0.46 U/ml) without any FXII clotting activity (<0.01 U/ml). The variant FXII in this plasma, denoted as FXII Locarno, was partially characterized by immunological and functional studies on the proposita’s plasma. FXII Locarno is a single chain molecule with the same size (M r = 80 kDa) as normal FXII. Isoelectric focusing suggested an excess of negative charge in the variant FXII as compared to normal FXII. In contrast to FXII in normal plasma, FXII Locarno was not proteolytically cleaved upon prolonged incubation of proposita’s plasma with dextran sulfate. Adsorption to kaolin was similar for both, abnormal and normal FXII. Incubation of the proposita’s plasma with dextran sulfate and exogenous plasma kallikrein showed normal cleavage of FXII Locarno outside of the tentative disulfide loop Cys340-Cys467, but only partial cleavage within this disulfide loop. Furthermore, plasma kallikrein-cleaved abnormal FXII showed neither amidolytic activity nor proteolytic activity against factor XI and plasma prekallikrein.These results suggest a structural alteration of FXII Locarno, affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII (a-FXIIa).

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