PDBsum entry 3ewe

Protein transport,structural protein

PDB id

3ewe

Contents

			Protein chains

					255 a.a.


					395 a.a.

References listed in PDB file

Key reference

Title

Structural evidence for common ancestry of the nuclear pore complex and vesicle coats.

Authors

S.G.Brohawn, N.C.Leksa, E.D.Spear, K.R.Rajashankar, T.U.Schwartz.

Ref.

Science, 2008, 322, 1369-1373. [DOI no: 10.1126/science.1165886]

PubMed id

18974315

Abstract

Nuclear pore complexes (NPCs) facilitate nucleocytoplasmic transport. These massive assemblies comprise an eightfold symmetric scaffold of architectural proteins and central-channel phenylalanine-glycine-repeat proteins forming the transport barrier. We determined the nucleoporin 85 (Nup85)*Seh1 structure, a module in the heptameric Nup84 complex, at 3.5 angstroms resolution. Structural, biochemical, and genetic analyses position the Nup84 complex in two peripheral NPC rings. We establish a conserved tripartite element, the ancestral coatomer element ACE1, that reoccurs in several nucleoporins and vesicle coat proteins, providing structural evidence of coevolution from a common ancestor. We identified interactions that define the organization of the Nup84 complex on the basis of comparison with vesicle coats and confirmed the sites by mutagenesis. We propose that the NPC scaffold, like vesicle coats, is composed of polygons with vertices and edges forming a membrane-proximal lattice that provides docking sites for additional nucleoporins.



	Figure 4. Fig. 4. Architecture of ACE1. (A) ACE1 containing proteins are shown as cylinders and sheets. Crowns are shown in blue, trunks in orange, tails in green, and other domains in gray. Modules with predicted structures are shown half-transparent. [PDB codes are 2QX5 for Nic96; 3BG1, Nup145C; 3CQC, Nup107 (Nup84 homolog); and 2PM6, Sec31] (B) Cartoons illustrating the similarity and modular nature of the ACE1 element. The N-terminal elaborations are, for Nic96, a coiled-coil domain that interacts with the Nsp1 complex; for Nup85, the Seh1-interacting insertion blade; for Nup145C, the Sec13-interacting insertion blade preceded by an autocatalytic cleavage domain and Nup145N; and, for Sec31, the Sec13-interacting insertion blade is preceded by its own N-terminal seven-bladed β propeller. Sec31 has a unique proline-rich insertion C-terminal to its trunk module followed by a conserved region predicted to be -helical.		Figure 5. Fig. 5. Lattice model for the Nup84 complex and the structural scaffold of the NPC. The ACE1 proteins Nup85, Nup145C, Nup84, Sec31, and Nic96 are colored according to Fig. 4. (A) Schematic diagram of COPII outer coat organization. The Sec31 Sec13 cuboctahedron composed of 24 edge elements (Sec31 Sec13 heterotetramers) is shown unwrapped and laid flat in two dimensions. The Sec31 Sec31 crown-crown interactions make edge elements, whereas propeller-propeller interactions are vertex elements (31). (B) Schematic diagram of the predicted latticelike organization of the structural scaffold of the NPC. The entire scaffold (eight spokes) is illustrated unwrapped and laid flat in two dimensions. The Nup84 complex comprises the nuclear and cytoplasmic rings, whereas the Nic96-containing complex makes up the inner ring. The relative position and interactions between the seven proteins in the Nup84 complex are shown with Sec13, Seh1, Nup133, and Nup120 colored in gray. The remainder of the Nic96 complex (Nup157/170, Nup188, and Nup192) is illustrated in gray. The illustration is not meant to predict relative positions of proteins or structure of the inner ring per se but shows the latticelike organization of the structural scaffold that is similar to vesicle coating complexes.

PROCHECK

	Headers