Structure and nuclear transport mechanism of HSP70 nuclear transporter, Hikeshi

Translocation of macromolecules across the nuclear membrane under the normal conditions has been well studied, but the mechanism of nuclear translocation under the heat-shock stress conditions remain elusive. Hikeshi is a nuclear transport receptor required for cell survival after heat-shock stress. It is in charge of heat shock-induced nuclear import of 70-kilodalton heat shock proteins (HSP70s) through interactions with FG repeats in nuclear pore complexes. Hikeshi forms an “asymmetric” homodimer that is a characteristic feature. Asymmetry of Hikeshi arises from the distinct conformation of the C-terminal domain and the flexibility of the linker regions which areas are essential for nuclear import of HSP70. A unique extended-loop (E-loop) in the N-terminal domain controls the interactions of Hikeshi with FG-Nups by opening or closing the F97 binding site. The recently reported X-ray structure of Hikeshi explains how Hikeshi participates in the nuclear import regulation through FG-Nups recognition, and which part of Hikeshi affects its binding to HSP70. In this review, we will discuss the structural insight on the highly unique import receptor Hikeshi in heat-shock stress condition.