RSS

PDB:3BG0

Protein Name

Sec13-Nup145C hetero-octamer (Architecture of a coat for the nuclear pore)

Species

human (Sec13), yeast (Nup145C)

Biological Context

The nuclear pore complex (NPC) mediates the passage of macromolecules between the nucleus and cytoplasm. The NPC, for example, passes synthesized RNAs from nucleus to cytoplasm, translated nuclear proteins from cytoplasm to nucleus, and shuttle proteins between them. It is one of the largest supramolecular assemblies in the eukaryotic cell, composed of about 30 different proteins termed nucleoporins (nups). Although the NPC is essential for the eukaryotic cell, its details are still unknown because of its large dimensions.

Electron microscopic reconstructions have revealed that the NPC is a cylindrical structure across the nuclear envelope. It consists of a central core with eight-fold rotational symmetry across a nucleocytoplasmic axis and two-fold symmetry in the plane of the nuclear envelope (Beck et al., 2004). Besides, a heptameric Nup84 complex is reported as one of subcomplexes of the NPC (Fig 1, Lutzmann et al., 2002). Besides those evidences and this crystal structure, the Nup84 heptamer may work as a part of a “coat” for the curvature between the inner and outer nuclear membrane, that is, the pore membrane domain of the nuclear envelope.

seven_nups (Fig. 1) Schematic representation of the Nup84 heptameric complex
The Nup84 heptamer is one of NPC subcomplexes. This schematic representation was reconstructed from electron microscopic images (Lutzmann et al., 2002).

The Sec13-Nup145 dimer region is colored blue.

Structure Description

3bg03bg0_x3bg0_y

A crystal structure of Sec13-Nup145C hetero-octamer has been determined. It forms a slightly bent rod structure with 285Å length, and has three pseudo-two-fold axes of symmetry. The central symmetry axis is in the Sec13 homodimer. And the adjacent two axes of symmetry are in the Nup145C homodimers. Nup145C has a novel fold in the form of a U-shaped structure. Sec13 contains a six-bladed β-propeller. The N-terminal domain of Nup145C has three β strands which are inserted into Sec13’s β-propeller fold, complementing it with a seventh blade (Fig. 3).

hetero_octamer (Fig. 2) Sec13-Nup145C hetero-octamer
Ribbon representation of the Sec13-Nup145C hetero-octamer, showing Sec13 in yellow and orange and Nup145C in green and blue. A 90-degree rotated view is shown on the right.

The three pseudo-two-fold axes exist within a Sec13 heterodimer (yellow) and two Nup145C heterodimers (green, blue).
beta_propeller (Fig. 3) β-propeller
Sec13's β-propeller (yellow) interacts with the N terminus of Nup145C (blue). Sec13 has six blades and each blade consists of four β strands. The three β strands in the N terminus of Nup145C are inserted in the propeller as the seventh blade.

With the hetero-octamer and evidences from electron microscopic study (Beck et al., 2004), an NPC core model was proposed. The eight Nup84 heptamers (Fig. 1) make a ring in a head-to-tail fashion and the rings are stacked on top of each other in an antiparallel manner. Thus, a cylindrical structure composed of four stacked rings is constructed (Fig. 4). At the same time, the formation of Sec13-Nup145C hetero-octamer across the four rings fixes them. Moreover, it is estimated that there exist an adapter cylinder and a channel cylinder within the coat cylinder concentrically.

model_of_NPC_core (Fig. 4) Model of the NPC core
A model of the NPC core as a series of concentric cylinders. This figure represents a model of the coat cylinder.

The eight Nup84 heptamers are circumferentially arranged in a head-to-tail fashion in four stacked rings. The Sec13-Nup145C hetero-octamers (blue) serve as vertical poles connecting the four fings. Red boxes and arrows show positions and orientations of Nup84 heptamers. Black box shows a hetero-octamer. The estimated diameter of the cylinder is about 1000Å.

Protein Data Bank (PDB)

References

Source

  • Hsia, K.C. Stavropoulos, P. Blobel, G. Hoelz, A.; "Architecture of a coat for the nuclear pore membrane."; Cell(Cambridge,Mass.); (2007) 131:1313-1326 PubMed:18160040.

Others

author: Naoya Fujita


Japanese version:PDB:3BG0