A year in structural signaling: mTOR-the PIKK of the bunch?

The phosphatidylinositol 3-kinase-like protein kinases (PIKKs) are large, atypical serine-threonine kinases that function in many important cellular signaling processes. Despite their prominence, and due to the complexity of their architecture and interactions, PIKKs have long managed to evade high-resolution crystallographic analysis. Recent, near-atomic-resolution structures of nucleotide- and inhibitor-bound complexes of a large carboxyl-terminal fragment of mammalian target of rapamycin (mTOR) are set to transform our understanding of the expansive signaling functions of these fascinating molecules and inform efforts to design therapeutic agents against a broad spectrum of human diseases ranging from diabetes to cancer.