Recognition of nuclear targeting signals by Karyopherin-β proteins

The Karyopherin-beta family of nuclear transport factors mediates the majority of nucleocytoplasmic transport. Although each of the 19 Karyopherin-beta s transports unique sets of cargos, only three classes of nuclear localization and export signals, or NLSs and NESs, have been characterized. The short basic classical-NLS was first discovered in the 1980s and their karyopherin-bound structures were first reported more than 10 years ago. More recently, structural and biophysical studies of Karyopherin-beta 2-cargo complexes led to definition of the complex and diverse PY-NLS. Structural knowledge of the leucine-rich NES is finally available more than 10 years after the discovery of its recognition by the exportin CRM1. We review recent findings relating to how these three classes of nuclear targeting signals are recognized by their Karyopherin-beta nuclear transport factors.