Structural basis for the antifolding activity of a molecular chaperone

Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone. The solution structure of SecB, a molecular chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. It's a wrap for chaperoned proteins Molecular chaperones are ubiquitous in the cell and are essential for maintaining a functional proteome, preventing protein misfolding, aggregation or premature folding by accelerating or delaying folding of their client proteins through mechanisms that are largely unknown. Here Charalampos Kalodimos and colleagues report the solution structure of SecB, a molecular chaperone with a strong antifolding activity, in complexes with two client proteins captured in the unfolded state. The structures reveal that multiple regions of non-native client proteins recognize long, continuous hydrophobic grooves on the surface of SecB, and then wrap themselves around the molecular chaperone.