Importin

Importins are transport proteins at the nuclear pore complex, needed for the selective import of proteins into the nucleus. They recognize nuclear localization signal sequences of cargo proteins. 

Sequence of amino acids that determine the transport of proteins into the nucleus. Although there is no clear consensus, nuclear localization signals tend to be rich in positively charged residues, which allow interaction with proteins from the nuclear import machinery (i.e., importins). 

IMPORTINS EXPORTINS ARE INVOLVED IN TRANSPORT OF MACROMOLECULES IN OUT OF THE NUCLEUS... 

Proteins similar to importins, referred to as ex-portins, are involved in export of many macromolecules from the nucleus. Cargo molecules for export carry nuclear export signals (NESs). Ran proteins are involved in this process also, and it is now established that the processes of import and export share a number of common feamres. 

Ran interacts with transport receptors which load and unload their cargo in the respective compartment depending on the nucleotide state of Ran [138]. An importin binds its cargo initially in the cytoplasm, gets translocated through the NPC, releases the cargo upon binding Ran GTP in the nucleus [139-141], and returns to the cytoplasm as a Ran GTP complex. The removal of Ran GTP... 

Binding of substrates to exportins is regulated in a converse manner to importins. Exportins bind their cargoes preferentially in the nucleus, forming a trimeric cargo exportin Ran GTP complex [142]. This trimeric complex is then transferred to the cytoplasm where Ran GTP is converted to Ran GDP. This results in Ran s dissociation from the complex, allowing the exportin to release its substrate, re-enter the nucleus, and to start the next export cycle. 

Fig. 3. Three-dimensional structures of three examples of superstructures formed by sequence repeats a linear rod (the spectrin a-chain dimer [PDB 2spc]), a superhelix of repeats (armadillo repeats of importin a-subunit [PDB lbk5]), and a closed /3-propeller (WD40 repeats from a fragment of the /3-subunit of the guanine nucleotide binding protein 1 [PDB lgg2 chain B]).

Simple basic NLS SV40 type a stretch rich in basic residues and often in proline residues Importin /3/importin a family... 

STAT 1) Uncharacterized requires phosphorylation of Tyr and dimerization Importin /8/NPI-l... 

U snRNPs) Sm proteins and trimethylguanosine Gap structure of RNA Importin /3/Snurportin... 

Nuclear import - STAT3, Importin, POPl Activation... 

Figure 4 Transfer of DNA from cytoplasm into the nucleoplasm. The DNA-containing complex can enter the nucleus by (1) crossing the membrane during mitotic nuclear membrane breakdown (2) diffusion through nuclear pore for small particles and (3) targeted uptake through the nuclear pore, facilitated by a nuclear localization sequence. Abbreviations NLS, nuclear localization sequence IMP, importin.

Truant R, Cullen BR. The arginine-rich domains present in human immunodeficiency virus type 1 TAT and Rev function as direct importin beta-dependent nuclear localization signals. Mol Cell Biol 1999 19(2) 1210-1217. 

The nuclear envelope is perforated with huge macromolecular assemblies of 30 different proteins that form nuclear pore complexes with a central channel of 25-30 nm in diameter. This channel allows proteins smaller than 30 kDa to passively traverse the outer and inner nuclear membranes. Larger proteins are actively transported across the nuclear envelope and contain nuclear localization signal (NLS) sequence motifs. These signals consist of one or two clusters of four or five basic residues localized usually within the polypeptide chain. The import of proteins with NLS through the channel is facilitated by the carrier heterodimer of importin-a ( > (Gorlich and Kutay 1999 Pemberton and Paschal... 

Nuclear importation is mediated by a number of proteins that cycle between the cytosol and the nucleus (Fig. 27-37), including importin a and J8 and a small GTPase known as Ran. A heterodimer of importin a and J8 functions as a soluble receptor for proteins targeted to the nucleus, with the a subunit binding NLS-bearing... 

---