Subcellular compartmentalization allows for complex modes of gene regulation in eukaryotic cells. The regulated and active transport of macromolecules between different compartments promotes cellular homeostasis and often drives differentiation. Transport of molecules from the cytoplasm to the nucleus depends on a family of proteins called karyopherins, as known as importins. The karyopherin superfamily of transporters consists of importin α and importin β sub-groups. All the proteins within this karyopherin superfamily share tandem huntingtin, elongation factor 3, protein phosphatase 2A and mechanistic target of rapamycin (HEAT) repeats. These repeats allow these proteins to bind to various cargo proteins, which often, but not always, contain a nuclear localization signal within their peptide sequence. Karyopherins then transport these cargoes into the nucleus through nuclear pores. Another key component of the transport machinery is the small GTPase Ran. Cytoplasmic Ran is typically maintained in a GDP-bound state, while nuclear Ran binds GTP. This concentration gradient of GDP and GTP bound Ran provides a directional cue for transport of proteins between the cytoplasm and nucleus. Once importins enter the nucleus, high affinity interactions with RanGTP cause karyopherins to release their cargoes and recycle back to the cytoplasm. Here you can see a recent cryoEM structure of importin-9 complexed with RanGTP (PDB code: 8F7A)

#molecularart ... #immolecular ... #nucleus ... #pore ... #import ... #transport ... #importin ... #RanGTP ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint