THE CONSERVED AMINO-TERMINAL DOMAIN OF HSRP1-ALPHA IS ESSENTIAL FOR NUCLEAR-PROTEIN IMPORT

Nuclear proteins are targeted through the nuclear pore complex (NPC) i n an energy-dependent reaction. The import reaction is mediated by nuc lear localization sequences (NLS) in the substrate which are recognize d by heterodimeric cytoplasmic receptors. hSRP1 alpha is an NLS-bindin g subunit of the human NLS receptor complex and is complexed in vivo w ith a second subunit of 97 kDa (p97), We show here that a short aminot erminal domain in hSRP1 alpha is necessary and sufficient for its inte raction with p97. This domain is conserved in other SRP1-like proteins and its fusion to a cytoplasmic reporter protein is sufficient to pro mote complete nuclear import, circumventing the usual requirement for an NLS receptor interaction. The same aminoterminal domain inhibits im port of NLS-containing proteins when added to an in vitro nuclear tran sport assay, While full-length hSRP1 alpha is able to leave the nucleu s, the amino-terminal domain alone is not sufficient to promote exit. We conclude that hSRP1 alpha functions as an adaptor to tether NLS-con taining substrates to the protein import machinery.