Flexible Linker Region in Endophilin Structure Affects its Thermostability

Abstract

Proteins involved in endocytosis often adopt specific structures to couple with curved lipid membranes. The BAR protein family is a group of important proteins with crescent BAR domains that often bind to the neck of budding vesicles to narrow the neck before the final scission step. They also contain SH3 domains that further recruit downstream proteins, like dynamin. However, the role played by the the unstructured flexible linker between the BAR and SH3 domains has received little attention thus far. Recently linker regions in some endocytosis related proteins have been reported to also participate in downstream protein recruiting. Here, we focus our research on the important BAR protein, endophilin. We are interested in endophilin's behavior upon membrane binding as well as the potential role of its linker consisting of around fifty residues. Via truncations of the endophilin sequence, we studied the role of the linker. Interestingly, the unstructured linker seems to influence endophilin thermostability. We are able to localize this characteristic to a short region close to the BAR domain, which contains less than twenty residues.