Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations.

The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which is essential for infectivity. Insertion of E into the target membrane serves to anchor E and possibly also to disrupt local order within the membrane. Both aspects are likely to be affected by the depth of insertion, orientation of the trimer with respect to the membrane normal, and the interactions that form between trimer and membrane.

Method for measuring the unbinding energy of strongly-bound membrane-associated proteins.

We describe a new method to measure the activation energy for unbinding (enthalpy ΔH* and free energy ΔG*) of a strongly-bound membrane-associated protein from a lipid membrane. It is based on measuring the rate of release of a liposome-bound protein during centrifugation on a sucrose gradient as a function of time and temperature. The method is used to determine ΔH* and ΔG* for the soluble dengue virus envelope protein (sE) strongly bound to 80:20 POPC:POPG liposomes at pH5.

Hydrogen Exchange Mass Spectrometry of Proteins at Langmuir Monolayers.

Hydrogen exchange (HX) mass spectrometry (MS) is valuable for providing conformational information for proteins/peptides that are very difficult to analyze with other methods such as peripheral membrane proteins and peptides that interact with membranes. We developed a new type of HX MS measurement that integrates Langmuir monolayers. A lipid monolayer was generated, a peptide or protein associated with it, and then the monolayer-associated peptide or protein was exposed to deuterium.

Membrane-mediated neuroprotection by curcumin from amyloid-β-peptide-induced toxicity.

Amyloid-β peptide (Aβ)-membrane interactions have been implicated in the formation of toxic oligomers that permeabilize membranes, allowing an influx of calcium ions and triggering cell death in the pathogenesis of Alzheimer's disease (AD). Curcumin, a small dietary polyphenolic molecule, has been shown to reduce Aβ-induced toxicity and AD pathology. We investigate here the effect of curcumin on Aβ40-induced toxicity in cultured human neuroblastoma SH-SY5Y cells and test a novel neuroprotection mechanism in which curcumin reduces Aβ-membrane interactions and attenuates Aβ-induced membrane disruptions.

Addition of a carbohydrate-binding module enhances cellulase penetration into cellulose substrates.

Introduction: Cellulases are of great interest for application in biomass degradation, yet the molecular details of the mode of action of glycoside hydrolases during degradation of insoluble cellulose remain elusive. To further improve these enzymes for application at industrial conditions, it is critical to gain a better understanding of not only the details of the degradation process, but also the function of accessory modules.

Method: We fused a carbohydrate-binding module (CBM) from family 2a to two thermophilic endoglucanases.

Interaction of tau protein with model lipid membranes induces tau structural compaction and membrane disruption.

The misfolding and aggregation of the intrinsically disordered, microtubule-associated tau protein into neurofibrillary tangles is implicated in the pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation and toxicity remain unknown. Recent work has shown that anionic lipid membranes can induce tau aggregation and that membrane permeabilization may serve as a pathway by which protein aggregates exert toxicity, suggesting that the plasma membrane may play dual roles in tau pathology.