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PDB:1XIP

Protein Name

N-terminal Domain of Nucleoporin Nup159

Species

Saccharomyces cerevisiae (Baker's yeast)

Biological Context

The nucleus is defined and separated from the cytoplasm by a nuclear envelope. It prevents the uncontrolled passage of molecules to and from the cytoplasm. Still, gene expression and cell regulation require that proteins and RNA are shipped across the envelope. This is a rather complex process that includes a large number of binding receptors and factors that over multistep reactions help for their import and export in native conformations. An enormous , ~125 MDa membrane spanning channel of protein aggregates called Nuclear Pore Complexes (NPC) offer the needed 'bypass' for this transport. NPC comprises around 150 proteins called nucleoporins (Nups), and exhibits an 8-fold symmetry. The nucleoplasmic side of NPC has a wide open 'bowl' shape connected to the cytoplasmic fibrils by a central channel. Export of mRNA through the channel requires that it is first bound to different binding proteins. These complexes are then transported across the NPC channel by interactions with phenylalanine-glycine residue motifs lining the channel interior. Although the processes of mRNA-protein complexes remodeling at the cytoplasmic end on NPC are not very well understood, several Nups have been identified as being indispensable for binding passing complexes, and thus taking active part in the mRNA transport. One of these nuclear pore proteins, Nup159, is known to be responsible for 'catching' Dbp5 helicases, which in turn participate in the catalytic modification of the transported mRNA-protein complexes. Although Nup159 consists of ~1500 residues only the first ~400 residues, the so called N-terminal domain, NTD, are actively binding the Dbp5 molecules.

Structure Description

1xip1xip_x1xip_y

The structure of the NTD of Nup159 is shown here. We can clearly see a well defined 60/50/50A beta-propeller, formed of seven blades. Each of the blades is formed by four anti-parallel beta-strands (A~D). Nup159 NTDs from all eukaryotes form seven-bladed beta-propellers and show conserved overall topology. Still, the yeast NTD differs in several ways. First, the sequences of the seven blades are very different from each other. Second, the NTD is asymmetric around the central axis. The beta-strand arrangements within the blades are similar, but the intervening loops are the ones responsible for the asymmetry. The third unusual structure property is the arrangement of the loop regions. The first four blades are connected by 1~4 residue long loops, while the loops connecting blades 5~7 are much longer - 15~20 residues. The loop that links blades 6 and 7 contains two surface residues, V323 and I326, that are crucial for the Dbp5-NTD complex formation. It is interesting to know that even if NTD is removed from Nup159, mRNA is still exported at levels sufficient to support growth.

Protein Data Bank (PDB)

References

Source

Weirich, C.S. Erzberger, J.P. Berger, J.M. Weis, K.; "The N-Terminal Domain of Nup159 Forms a beta-Propeller that Functions in mRNA Export by Tethering the Helicase Dbp5 to the Nuclear Pore"; Mol.Cell; (2004) 16:749-760 PubMed:15574330.

Others

UniProt:P40477

author: Rossen Apostolov


Japanese version:PDB:1XIP