Clustering of tetrameric influenza M2 peptides in lipid bilayers investigated by F solid-state NMR.

The influenza M2 protein forms a drug-targeted tetrameric proton channel to mediate virus uncoating, and carries out membrane scission to enable virus release. While the proton channel function of M2 has been extensively studied, the mechanism by which M2 catalyzes membrane scission is still not well understood. Previous fluorescence and electron microscopy studies indicated that M2 tetramers concentrate at the neck of the budding virus in the host plasma membrane.

Cholesterol-Mediated Clustering of the HIV Fusion Protein gp41 in Lipid Bilayers.

The envelope glycoprotein (Env) of the human immunodeficient virus (HIV-1) is known to cluster on the viral membrane surface to attach to target cells and cause membrane fusion for HIV-1 infection. However, the molecular structural mechanisms that drive Env clustering remain opaque. Here, we use solid-state NMR spectroscopy and molecular dynamics (MD) simulations to investigate nanometer-scale clustering of the membrane-proximal external region (MPER) and transmembrane domain (TMD) of gp41, the fusion protein component of Env.

Interactions of HIV gp41's membrane-proximal external region and transmembrane domain with phospholipid membranes from P NMR.

HIV-1 entry into cells requires coordinated changes of the conformation and dynamics of both the fusion protein, gp41, and the lipids in the cell membrane and virus envelope. Commonly proposed features of membrane deformation during fusion include high membrane curvature, lipid disorder, and membrane surface dehydration. The virus envelope and target cell membrane contain a diverse set of phospholipids and cholesterol.

Cargo engagement protects protease adaptors from degradation in a substrate-specific manner.

Protein degradation in bacteria is a highly controlled process involving proteolytic adaptors that regulate protein degradation during cell cycle progression or during stress responses. Many adaptors work as scaffolds that selectively bind cargo and tether substrates to their cognate proteases to promote substrate destruction, whereas others primarily activate the target protease. Because adaptors must bind their cognate protease, all adaptors run the risk of being recognized by the protease as substrates themselves, a process that could limit their effectiveness.