Sec13-Nup145C hetero-octamer (Architecture of a coat for the nuclear pore)
human (Sec13), yeast (Nup145C)
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.
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).
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.
Protein Data Bank (PDB)
author: Naoya Fujita