STRUCTURE AND PLASTICITY OF PERIPHERAL MEMBRANE PROTEINS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The presence of various domains in signaling proteins with affinity for phospholipids suggests that signaling reactions and protein conformations are likely to be modulated by membrane interactions. Cellular membranes are highly dynamic structures that change their shape during events such as vesicle budding and cell migration, and serve as signaling platforms during such processes. These cellular events are crucial for down-regulation of cell surface receptors, recycling of membrane proteins and many other housekeeping functions in cell metabolism and signaling. A binding module with preference for deformed membranes, the BAR (Bin-Amphiphysin-Rvs) domain, has been described only recently. This domain appears in the context of a large variety of multi-domain signaling proteins, and we speculate that membrane binding might alter the activities of neighboring domains and the overall conformation of these proteins. To get at the apo-state in the absence of membranes, we wish to determine the structures of multi-domain BAR domain-containing proteins, specifically focusing on Sorting nexin 9 and Endophilin. Both proteins are adaptor proteins that bind Dynamin and other proteins involved in membrane trafficking and fission. The structures will be used to design approaches that will allow us to study conformational changes and overall plasticity of these proteins in solution and on model membranes.