Prediction of structural domains of TAP reveals details of its interactionwith p15 and nucleoporins

Vertebrate TAP is a nuclear mRNA export factor homologous to yeast Mex67p. The middle domain of TAP binds directly to p15, a protein related to the nu clear transport factor 2 (NTF2), whereas its C-terminal domain interacts wi th various nucleoporins, the components of the nuclear pore complex (NPC). Here, we report that the middle domain of TAP is also similar to NTF2, as w ell as to regions in Ras-GAP SH3 domain binding protein (G3BP) and some pla nt protein kinases. Based on the known three-dimensional structure of NTF2. homodimer, a heterodimerization model of TAP and p15 could be inferred. Th is model was confirmed by site-directed mutagenesis of residues located at the dimerinterface. Furthermore, the C-terminus of TAP was found to contain a ubiquitin-associated (UBA) domain. By site-directed mutagenesis we show that a conserved loop in this domain plays an essential role in mediating T AP-nucleoporin interaction.