The endothelial cell protein C receptor (EPCR) functions as an important regulator of the anticoagulant pathway by binding and enhancing activation thrombin-thrombomodulin complex. EPCR binds to both activated (APC) with high affinity. A soluble form (sEPCR) circulates in plasma inhibits APC activity. In this study, we investigate mechanisms which sEPCR modulates function. Soluble inhibited inactivation factor Va only presence phospholipid vesicles. By using flow cytometric analysis 3...

Alveolar type II epithelial cell (ATII) apoptosis and proliferation of mesenchymal cells are the hallmarks idiopathic pulmonary fibrosis, a devastating disease unknown cause characterized by alveolar injury progressive fibrosis. We used mouse model bleomycin (BLM)-induced lung to understand involvement p53-mediated changes in urokinase-type plasminogen activator (uPA) inhibitor-1 (PAI-1) levels regulation injury. found marked induction p53 ATII from mice exposed BLM. Transgenic expressing...

Tissue factor (TF), an integral membrane protein, enhances the feedback activation of VI1 by VIIa (factor autoactivation).We found that, in contrast to other known membrane-dependent coagulation reactions, TF-dependent autoactivation occurred preferentially on neutral phospholipid vesicles relative negatively charged containing phosphatidylserine.This reaction was best described a novel mechanism which enzyme and substrate are each bound separate cofactor (TF) molecules.This unusual...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphatidylethanolamine augments factor VIIa-tissue activity: enhancement of sensitivity to phosphatidylserinePierre F. Neuenschwander, Emma Bianco-Fisher, Alireza R. Rezaie, and James H. MorrisseyCite this: Biochemistry 1995, 34, 43, 13988–13993Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October...

The activation of human blood coagulation factor VII can occur by the feedback activity either VIIa (autoactivation) or Xa. Both these reactions are known to be enhanced presence tissue factor, an integral membrane protein and cofactor for VIIa. We examine here 125I-factor both Xa employing a mutant soluble form which has had its transmembrane cytoplasmic domains deleted (sTF1-219). This retains toward in single-stage clotting assay but shows strong dependence on initial plasma levels (from...

The roles of the putative membrane-interactive regions factor VIIa (fVIIa) and tissue (TF) have been examined.Enzymatic removal 4-carboxyglutamic acid (Gla) domain fVIIa had no effect on hydrolysis a tripeptidyl chromogenic substrate in absence or presence TF.Additionally, Gla-domainless (GdVIIa) was similar to native activating X TF phospholipid.However, GdVIIa complex with recombinant soluble (sTF) 76-fold less efficient activation than fVIIa.sTF.The difference increased 740-fold using...

Seasonal and especially pandemic influenza predispose patients to secondary bacterial pneumonias, which are a major cause of deaths morbidity. Staphylococcus aureus is particularly common deadly form post-influenza pneumonia, increasing staphylococcal drug resistance makes the development new therapies urgent. We explored an innate immune-mediated model lung define novel mechanisms by host can be protected against pneumonia after sub-lethal infection. found that stimulating immunity in...

Beginning from the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic swept all over world and is still afflicting whole global population. Given that vaccine-manufacturing ability limited virus can evolve quickly, vaccination alone may not be able to pandemic, thus developing fast accurate diagnoses effective therapeutics will always unmet needs. Phage display peptide library has been used in screening antigen-specific peptides for invention novel mimic...

BackgroundAdherence to antiretroviral therapy (ART) remains a challenge for many people with HIV and was exacerbated during the COVID-19 pandemic. This paper examines factors associated ART adherence among who inject drugs (PWHWID) in Almaty, Kazakhstan pandemic.MethodsA cross-sectional survey conducted from October 2020 August 2022 66 PWHWID their treatment support partners (n = 66) assess associations between sociodemographic, related, social support, other factors. Multilevel generalized...

The topography of membrane-bound blood coagulation factor VIIa (fVIIa) was examined by positioning a fluorescein dye in the active site fVIIa via tripeptide tether to yield fluorescein-D-phenylalanyl-L-prolyl-L-arginyl-fVIIa (Fl-FPR-fVIIa). location active-site probe relative membrane surface determined, both presence and absence tissue (TF), using fluorescence energy transfer between octadecylrhodamine (OR) at phospholipid vesicle surface. When Fl-FPR-fVIIa titrated with vesicles containing...

Early secreted antigenic target of 6 kDa (ESAT-6) Mycobacterium tuberculosis is a T cell Ag that potential vaccine candidate, but it also virulence factor mediates pathogenicity. To better understand the effects ESAT-6 on immune response, we studied effect human dendritic cells (DCs). Peripheral blood monocytes were treated with GM-CSF and IL-4 to yield immature DCs, which matured by addition LPS CD40 ligand (CD40L), or without ESAT-6. inhibited LPS/CD40L-induced DC expression costimulatory...

Background Since adaptive immunity is thought to be central against influenza A virus (IAV) pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift circulating viruses. Recent studies highlighted the importance innate protecting influenza. Methods Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes maturation mononuclear phagocytes, enhancing their capacity for...

Tissue factor (TF), an integral membrane protein, is the cofactor for serine protease, coagulation VIIa (FVIIa).Previous studies of isolated extracellular domain TF (sTF) reported a kcat X (FX) activation by sTF-VIIa complex only 4% that wildtype TF-VIIa and furthermore, complete inability s T F to support FVII autoactivation.W e now report in presence poly(Clysine), sTF promoted both FX autoactivation, latter with apparent second-order rate constant higher than previously wild-type...

Upon activation, factor X participates in the prothrombin activation complex. Similar to 4-carboxyglutamic acid (Gla)-domainless protein C, Gla-domainless (GDFX) contains a high affinity Ca(2+)-binding site critical for function of these molecules. In case we recently demonstrated that is outside first epidermal growth (EGF) homology domain. To examine if this also true X, have expressed human 293 cells deletion mutant (E2FX) which lacks entire Gla region as well NH2-terminal EGF X. Direct...

The first enzyme in the blood clotting cascade consists of two distinct protein subunits: a catalytic subunit (factor VIIa; FVIIa) and an essential regulatory (tissue factor; TF). FVIIa is soluble plasma protease, while TF cell-surface, integral-membrane protein. recently reported X-ray crystal structure complex isolated extracellular domain has provided important insights into protein-protein interactions that bind these subunits together (1). Equally functioning TF-FVIIa complex, but much...

Summary Tissue factor (TF) markedly enhances the ability of VIIa (FVIIa) to cleave both macromolecular and small peptidyl substrates. Using soluble mutant TF (sTF) investigate TF-enhanced FVIIa amidolytic activity in solution, we screened thirty-four commercially available peptidyl-p-nitroanilide substrates found that substrate hydrolysis rates were influenced by peptide sequence N-terminal blocking group (MeSO2 > MeO-CO or free N-terminus >> benzoyl). Two (Chromozym t-PA:...

Oligomerization of the initiator protein, DnaA, on origin replication (oriC) is crucial for initiation DNA replication. Studies in Escherichia coli (Gram-negative) have revealed that binding DnaA to ATP, but not hydrolysis sufficient promote binding, oligomerization and strand separation. To begin understanding initial events involved Mycobacterium tuberculosis (Gram-positive), we investigated interactions M. (DnaA(TB)) with oriC using surface plasmon resonance presence ATP ADP. We provide...