Electrostatics Drive the Molecular Chaperone BiP to Preferentially Bind Oligomerized States of a Client Protein.

Hsp70 chaperones bind short monomeric peptides with a weak characteristic affinity in the low micromolar range, but can also bind some aggregates, fibrils, and amyloids, with low nanomolar affinity. While this differential affinity enables Hsp70 to preferentially target potentially toxic aggregates, it is unknown how a chaperone can differentiate between monomeric and aggregated states of a client protein and why preferential binding is only observed for some aggregated clients but not others. Here we examine the interaction of BiP (the Hsp70 paralog in the endoplasmic reticulum) with the client proIGF2, the pro-protein form of IGF2 that includes a long and mostly disordered E-peptide region that promotes proIGF2 oligomerization.

The shape of pleomorphic virions determines resistance to cell-entry pressure.

Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells.

Structural cavities are critical to balancing stability and activity of a membrane-integral enzyme.

Packing interaction is a critical driving force in the folding of helical membrane proteins. Despite the importance, packing defects (i.e.