research advances
December 2008 research highlight
Common ancestry of nuclear pore complex and vesicle-coat proteins
PSI-SGKB [doi:10.1038/rhlights_psisgkb.2008.19]
The crystal structure of two nucleoporins in complex suggests that the NPC scaffold has properties similar to those of vesicle coats.
Macromolecules cross the nuclear membrane through the nuclear pore complex (NPC). Although the structure of many of the individual protein components are known, the overall structure of the 40-60 MDa NPC is not clearly understood. Cryo-electron microscopy and cryo-electron tomography have provided a view of the NPC structure, but the low resolution of these techniques has prevented the fitting of the crystal structures. Now, the crystal structure of two nucleoporins in complex suggests that the NPC scaffold has properties similar to those of vesicle coats.
Several highly divergent scaffold proteins of the NPC and vesicle coats share a common domain, the ancestral coatamer element, ACE1, composed of crown, trunk and tail. (PDB 2QX5, 3EWE).
Of the approximately 30 nucleoporins that make up the NPC, only a few are stably attached to the complex. In the yeast Saccharomyces cerevisiae, the core proteins form two essential complexes: the heptameric Nup84 complex and the hetero-oligomeric Nic96-containing complex.
Thomas Schwartz and colleagues at MIT report the structure of two Nup84-complex proteins: residues 1–564 (of 744) of Nup85 bound to full-length Seh1 at 3.5 Å resolution. These Nup84 complex proteins form distinct units in a tightly associated complex. More striking though was the similarity in secondary-structure elements, three-dimensional folds and assembly between Nup85–Seh1 and another member of the Nup84 complex, Nup145C–Sec13.
Surprisingly, a comparison of Nup85 with nucleoporins Nic96, Nup84 and Nup145C reveals that they share three structural elements: a crown, a trunk and a tail. Further analysis turned up another protein with a similar structure, the coat component of the vesicle COPII, Sec31. The authors named this tripartite element the ancestral coatomer element, ACE1.
From this, Schwartz and colleagues propose that the NPC scaffold, in common with vesicle coats, is composed of polygons that form a lattice upon which additional NPC proteins can dock. The modular nature of vesicle coats provides flexibility in composition and size; NPCs might also benefit from this versatility.
