Chemical cross-linking, dynamic light scattering, sedimentation velocity, and electron microscopy analyses led to the conclusion that M2-1 forms a 5.4S tetramer of 89 kDa and similar to 7.6 nm in diameter at micromolar concentrations. By using a series of deletion mutants, the oligomerization domain of M2-1 was mapped

to a putative alpha-helix consisting of amino acid residues 32 to 63. When tested in an RSV minigenome replicon system using a luciferase gene as a reporter, an M2-1 deletion mutant lacking this region showed a significant reduction in RNA transcription compared to wild-type M2-1, indicating that M2-1 oligomerization Evofosfamide chemical structure is essential for the activity of the protein. We also show that the region encompassing amino acid residues 59 to 178 binds to PLX4032 cost P and RNA in a competitive manner that is independent of the phosphorylation status of M2-1.”
“Apolipoprotein

E (ApoE) 4 is a potent risk factor for Alzheimer’s disease (AD). However, the mechanism underlying ApoE4 function in the pathology of AD is not well understood. We report here that, in comparison with ApoE2 and ApoE3, ApoE4 significantly reduces levels of insulin-degrading enzyme (IDE), which is responsible for the cellular clearance of A beta in neurons. This differential regulation of IDE by various ApoE isoforms was blocked by coincubation with N-methyl-D-aspartic acid (NMDA) receptor inhibitors and receptor-associated protein (RAP), which blocked the interaction between ApoE and members of the low-density lipoprotein (LDL) receptor family. Moreover, inhibition of the NMDA receptor increased IDE levels in neurons, while activation of the NMDA receptor-reduced IDE expression. Further studies demonstrate that, as a pathway downstream of the NMDA receptor, CAMP-dependent protein kinase (PKA) contributes to the NMDA receptor-reduced IDE expression. These results suggest that ApoE4 down-regulates IDE expression in neurons by binding to its receptor and stimulating the NMDA receptor pathway, which may account for its role in AD pathogenesis. (C) 2009 Elsevier Ireland Ltd. All

rights reserved.”
“Hepatitis E virus (HEV) is the causative agent of hepatitis E, a major form of viral hepatitis in developing countries. The open reading frame 3 (ORF3) of HEV encodes a phosphoprotein with a molecular mass of approximately 13 kDa Sulfite dehydrogenase (hereinafter called vp13). vp13 is essential for establishing HEV infections in animals, yet its exact functions are still obscure. Our current study found evidence showing interaction between vp13 and microtubules. Live-cell confocal fluorescence microscopy revealed both filamentous and punctate distribution patterns of vp13 in cells transfected with recombinant ORF3 reporter plasmids. The filamentous pattern of vp13 was altered by a microtubule-destabilizing drug. The vp13 expression led to elevation of acetylated alpha-tubulin, indicating increased microtubule stability.