Thermodynamics of Binding Silver Ion to Jack Bean Urease

Abstract

Several studies suggest that tau in AD brains may exhibit abnormal interactions with the neuronal cell membrane. We hypothesize that the lipid membrane can mediate tau pathology by templating tau to misfold into an assembly-competent conformation and subsequently nucleating tau to aggregate into fibrils. We used lipid monolayers at the air/water interface as a model membrane to probe taumembrane interactions. We found that although tau (hTau40) is highly soluble and charged, it is also highly surface active. hTau40 exhibits strong association with negative DMPG lipids, while exhibiting weaker interactions with the positive DMTAP and neutral DMPC lipids. Thus, tau-membrane interactions are strongly mediated by electrostatic interactions. To identify the hTau40 domain that is responsible for its interaction with membranes, we measured the interaction between different tau constructs (K18 and K32) and lipid membranes. Additionally, X-ray scattering experiments were carried out to elucidate the structural details of tau associated with lipid membranes. Our data show that tau's C-terminal, microtubule binding domain, is responsible for its association with the lipid membrane and that these binding events disrupts the ordering and structure of the membrane. Our study suggests that the ''soft'' nature of tau can give rise to rich dynamic behaviors at interfaces, such as the physiological lipid membrane interface. Our data implicate that the inner leaflet of the cell membrane, enriched in negatively charged lipids, can potentially recruit tau in the cytoplasm, which may be critical in initiating the cascade of pathogenic misfolding and aggregation events in AD.