The Structure of Importin-ß Bound to SREBP-2: Nuclear Import of a Transcription Factor

Abstract

The sterol regulatory element-binding protein 2 (SREBP-2), a nuclear transcription factor that is essential for cholesterol metabolism, enters the nucleus through a direct interaction of its helix-loop-helix leucine zipper domain with importin-beta. We show the crystal structure of importin-beta complexed with the active form of SREBP-2. Importin-beta uses characteristic long helices like a pair of chopsticks to interact with an SREBP-2 dimer. Importin-beta changes its conformation to reveal a pseudo-twofold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule. Importin-beta may use a similar strategy to recognize other dimeric cargoes.

Structural Requirements for Sterol Regulatory Element-binding Protein (SREBP) Cleavage in Fission Yeast

“…We verified that the N terminus of GFP-Sre2 aa 423-793 translocates to the nucleus, demonstrating that Sre2-MS is functionally imported after Dsc-dependent cleavage (data not shown). These data are consistent with studies on mammalian SREBP-2 showing that the bHLHzip domain functions as a nuclear import signal (21).…”

Interaction of the HIV-1 Intasome with Transportin 3 Protein (TNPO3 or TRN-SR2)

“…Indeed many of the key residues indentified in Importin-13 as directly binding RanGTP are also present in TNPO3 (51). The C-terminal portions of these karyopherins usually bind their respective cargos (69,(77)(78)(79)(80)(81)(82)(83). However, two exceptions have been reported with Ubc9 and parathyroid hormone-related protein interacting with the N-terminal arches of Importin-13 and Importin-␤, respectively (40,66).…”

IQGAP1 Protein Regulates Nuclear Localization of β-Catenin via Importin-β5 Protein in Wnt Signaling

“…Importin-␤ genes also mediate the translocation of non-NLS proteins by directly binding to them (29). The transport direction of importin-␤-cargo complex is determined by the gradient of different nucleotide-bound states of a small GTPase, Ran.…”