Shank is a new family of master scaffolding proteins in the postsynaptic density of eukaryotic neurons that interacts with cytosolic and membrane proteins. Shanks amplify intracellular signals involved in neurite outgrowth, cell migration and cytoskeletal organization. Shanks contain a C-terminal sterile α motif (SAM) domain. SAM domains are discrete protein modules found in diverse eukaryotes and have been shown to form polymers. The wildtype Shank 3 SAM domain is insoluble due to polymerization. To disrupt polymerization and solubilize the domain, point mutations were made at all conserved but potentially exposed sites. Four different mutants were found to be soluble and have been crystallized. Electron microscopy has shown that one N-terminal mutant forms fibers, suggesting that Shank SAM domains can polymerize at the neuron membrane. Polymerization of Shank would allow associated proteins to be clustered and thus communicate and to amplify intracellular signals. Thanks to USPHS National Research Service Award GM07185.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.