2H4M: Karyopherin Beta2/transportin-m9nls

Karyopherinbeta (Kapbeta) proteins bind nuclear localization and export signals (NLSs and NESs) to mediate nucleocytoplasmic trafficking, a process regulated by Ran GTPase through its nucleotide cycle. Diversity and complexity of signals recognized by Kap betas have prevented prediction of new Kap beta substrates. The structure of Kap beta 2 (also known as Transportin) bound to one of its substrates, the NLS of hnRNP A1, that we report here explains the mechanism of substrate displacement by Ran GTPase. Further analyses reveal three rules for NLS recognition by Kap beta 2: NLSs are structurally disordered in free substrates, have overall basic character, and possess a central hydrophobic or basic motif followed by a C-terminal R/H/KX(2-5)PY consensus sequence. We demonstrate the predictive nature of these rules by identifying NLSs in seven previously known Kap beta 2 substrates and uncovering 81 new candidate substrates, confirming five experimentally. These studies define and validate a new NLS that could not be predicted by primary sequence analysis alone.
PDB ID: 2H4MDownload
MMDB ID: 53318
PDB Deposition Date: 2006/5/24
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 3.05  Å
Source Organism:
Similar Structures:
Biological Unit for 2H4M: tetrameric; determined by author
Molecular Components in 2H4M
Label Count Molecule
Proteins (4 molecules)
Transportin-1(Gene symbol: TNPO1)
Molecule annotation
Heterogeneous Nuclear Ribonucleoprotein A1(Gene symbol: HNRNPA1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB