THE BINDING-SITE OF KARYOPHERIN ALPHA FOR KARYOPHERIN-BETA OVERLAPS WITH A NUCLEAR-LOCALIZATION SEQUENCE

By using proteolysis, recombinant mutant proteins, or synthetic peptid es and by testing these reagents in liquid phase binding or nuclear im port assays, we have mapped binding regions of karyopherin alpha. We f ound that the C-terminal region of karyopherin alpha recognizes the nu clear localization sequence (NLS), whereas its N-terminal region binds karyopherin beta. Surprisingly, karyopherin a also contains an NLS, T hus, karyopherin a belongs to a group of proteins that contain both a ligand (NLS) and a cognate receptor (NLS recognition site) in one mole cule with a potential for autologous ligand-receptor interactions, The NLS of karyopherin alpha overlaps with the binding site of karyopheri n alpha for karyopherin beta. Hence, binding of karyopherin beta to ka ryopherin alpha covers the NLS of karyopherin alpha. This prevents aut ologous ligand receptor interactions and explains the observed coopera tive binding of karyopherin alpha to a heterologous NLS protein in the presence of karyopherin beta.