Protein–membrane interactions: blood clotting on nanoscale bilayers

Morrissey, James H.; Pureza, Vincent; Davis-Harrison, Rebecca L.; Sligar, Stephen G.; Rienstra, Chad M.; Kijac, Aleksandra; Ohkubo, Y. Zenmei; Tajkhorshid, Emad

doi:10.1111/j.1538-7836.2009.03390.x

Cited by 26 publications

(25 citation statements)

References 31 publications

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“…on the physical, chemical and biochemical properties in well-defined oligomeric states associated with the functioning of these proteins in biological systems. They have also have provided multiple opportunities for studying interactions of proteins with their surrounding lipids (33, 43, 54, 71–73) as well as interactions of membrane lipids and embedded proteins with soluble interacting proteins ( i.e ., blood coagulation factors) (64, 66, 74). Nanodiscs without any incorporated proteins have been also used as nanoscale mimics of the biomembrane surface and its interactions with soluble proteins and peptides (75).…”

Section: Nanodiscs For Analysis Of Lipid-protein Interactionsmentioning

confidence: 99%

“…Many of our previous Nanodisc assemblies have routinely used mixed lipids ranging in composition from 100% POPC to 100% POPS (66) and others have used mixtures of PA, PS, PE head groups in PC backgrounds to evaluate the role of these in controlling X, Y and Z (64, 66, 74). Extending these previous experiments to analysis of P450 systems, we co-assembled human CYP3A4 together with its P450 reductase and varying lipids in Nanodiscs and quantitated NADPH-driven testosterone hydroxylation.…”

Section: Nanodiscs For Analysis Of Lipid-protein Interactionsmentioning

confidence: 99%

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Nanodiscs as a New Tool to Examine Lipid–Protein Interactions

Schuler

Denisov

Sligar

2012

Methods in Molecular Biology

139

131

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Nanodiscs are self-assembled discoidal fragments of lipid bilayers 8 – 16 nm in diameter, stabilized in solution by amphipathic helical scaffold protein. As stable and highly soluble membrane mimetics with controlled lipid composition and ability to add affinity tags to the scaffold protein, Nanodiscs represent an attractive model system for solubilization, isolation, purification, and biophysical and biochemical studies of membrane proteins. We overview various approaches to the structural and functional studies of different classes of integral membrane proteins such as ion channels, transporters, GPCR and other receptors, membrane enzymes, blood coagulation cascade proteins, et cetera incorporated into Nanodiscs with the special focus on the advantages provided by homogeneity, ability to control oligomerization state of the target protein and lipid composition of the bilayer. Special attention is paid to the opportunities provided by Nanodisc system for the detailed studies of the role of different lipid properties and protein – lipid interactions in the functional behavior of membrane proteins.

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Section: Nanodiscs For Analysis Of Lipid-protein Interactionsmentioning

confidence: 99%

Section: Nanodiscs For Analysis Of Lipid-protein Interactionsmentioning

confidence: 99%

Nanodiscs as a New Tool to Examine Lipid–Protein Interactions

Schuler

Denisov

Sligar

2012

Methods in Molecular Biology

139

131

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“…Phosphatidylserine is sequestered on the inner leaflet of the bilayer, but becomes exposed when the membrane structure collapses by apoptosis and so on and is thought to be connected with TF de-encryption. Exposed phosphatidylserine appears to be connected with the activation of TF and FVlla complexes [7], and phosphatidylserine itself activates the coagulation cascade [9]. Therefore, increased phosphatidylserine exposure results in increased procoagulant activity (PCA).…”

Section: Introductionmentioning

confidence: 98%

Activation of coagulation by a thalidomide-based regimen

Hoshi

Matsumoto²,

Chung³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

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Combining thalidomide (Thal) with chemotherapeutic agents or steroid preparations led to improved response rates in the treatment of multiple myeloma. However, deep vein thrombosis (DVT) is one of the most serious side-effects noted with this regimen, and how a Thal-based regimen causes DVT is unclear. We investigated the procoagulant effects of Thal when combined with chemotherapeutic agents in vitro, focusing on tissue factor (TF) and phosphatidylserine. We examined the effects of the chemotherapeutic doxorubicin hydrochloride (Dox) and the steroid dexamethasone (Dex), with or without Thal. Our study used the human vascular endothelial, monocytic, and myeloma cell lines, EAhy926, THP-1, and RPMI8226, respectively. In EAhy926 and THP-1, Dex treatment increased expression of TF, which may induce procoagulant activity (PCA). Upregulation of TF mRNA correlated with activation of the Egr-1 pathway. In Thal and Dex treatments, the increase of PCA induction from phosphatidylserine exposure was modest. In contrast, Dox and Thal-Dox increased phosphatidylserine exposure in both cell types. In THP-1 cells, cell surface phosphatidylserine exposure correlated with increased PCA by Dox. Thal alone showed a modest increase in phosphatidylserine exposure in endothelial cells and monocytes. When Thal is given in combination with chemotherapies or Dex, endothelial cell and monocyte PCA may be induced through phosphatidylserine exposure, or TF expression. Induction may be protracted by Thal, which has an antiangiogenic activity. Therefore, prophylactic anticoagulant strategies should be considered in Thal-based combination regimens.

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“…Phosphatidylserine (PS) localizes at the inner leaflet of the bilayer, but becomes exposed if the membrane structure collapses by apoptosis and is thought to be connected with TF de-encryption [7]. PS activates the coagulation cascade [8]. Therefore, increased exposure to PS may result in upregulated procoagulant activity (PCA).…”

Section: Introductionmentioning

confidence: 99%

Activation of Coagulation by Lenalidomide-Based Regimens for the Treatment of Multiple Myeloma

et al. 2013

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We investigated the procoagulant effects of lenalidomide (Len)-based regimens in vitro focusing on tissue factor (TF) and phosphatidylserine (PS). We examined the effects of a pharmacological concentration of Len with or without the corticosteroid dexamethasone (Dex) and the proteasome inhibitor bortezomib (Bor) using the human vascular endothelial cell line EAhy926 and the monocytic cell lines THP-1 and U937. Cell-surface procoagulant activity (PCA) was induced by Dex-containing regimens in all lines. Expression of TF antigen on the cell surface and of TF mRNA was markedly increased by Dex-containing regimens. PS exposure was increased modestly by a Len-based regimen. PS exposure was increased modestly in EAhy926 cells, and markedly increased in THP-1 and U937 cells by Bor-containing treatment. An anti-TF monoclonal antibody almost completely blocked the induced PCA. When Len is given in combination with Dex, PCA may be induced on endothelial cells and monocytes through TF expression and PS exposure.

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Protein–membrane interactions: blood clotting on nanoscale bilayers

Cited by 26 publications

References 31 publications

Nanodiscs as a New Tool to Examine Lipid–Protein Interactions

Nanodiscs as a New Tool to Examine Lipid–Protein Interactions

Activation of coagulation by a thalidomide-based regimen

Activation of Coagulation by Lenalidomide-Based Regimens for the Treatment of Multiple Myeloma

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