Atomic structure of the Y complex of the nuclear pore

Abstract

The nuclear pore complex (NPC) is the principal gateway for transport into and out of the nucleus. Selectivity is achieved through the hydrogel-like core of the NPC. The structural integrity of the NPC depends on ~15 architectural proteins, which are organized in distinct subcomplexes to form the >40 MDa ring-like structure. Here we present the 4.1 Å crystal structure of a heterotetrameric core element (‘hub’) of the Y-complex, the essential NPC building block, from Myceliophthora thermophila. Using the ‘hub’ structure together with known Y-complex fragments we built the entire ~0.5 MDa Y-complex. Our data reveal that the conserved core of the Y-complex has 6, rather than 7 members. Evolutionarily distant Y-complex assemblies share a conserved core that is very similar in shape and dimension, suggesting that there are closely related architectural codes for constructing the NPC in all eukaryotes.

Systematic Protein–Protein Interaction Analysis Reveals Intersubcomplex Contacts in the Nuclear Pore Complex

“…In contrast, the crown-trunk domain of scNup145C (aa 178 -555) interacted with scNup84 (31,32). The scNup85 tail (aa 533-744) also interacted directly with full-length scNup145C, as previously shown for various species (9,10,33). Four additional complexes for which crystal structures exist tested positive in our screen: scNsp1-Nup57; scNup57-Nup49; scNup82-Nup159; scNup82-Nup116 (34,35) (Fig.…”

“…Thus, in principle, some of the intracomplex interactions may contribute as intercomplex interaction in the assembled pore, but it is difficult to make this distinction from the Y2H interaction data alone. With the elucidation of the Nup120 -Nup145C-Sec13-Nup85 Y-complex hub structure, it was possible to assemble a composite 3D atomic model of this subcomplex (9). Because our Y2H data perfectly reflect all interactions in the subcomplex at domain resolution (Fig.…”

“…Because of the resolution gap between the crystal structures and the tomographic reconstructions and an incomplete set of available crystal structures, obtained from a variety of evolutionarily distant species, docking approaches are still incomplete (9,10,18). This is further complicated by the paucity of intersubcomplex interaction data (12, 18 -21).…”

Crystal structure of human nuclear pore complex component NUP43

“…Most of the loop residues are invisible and the length of the loop varies among Nup43 orthologs. In contrast, another loop between b1A and b1B (resi [19][20][21][22][23][24][25][26][27][28][29][30], exhibits an ordered conformation in the crystal structure. It is solvent accessible and protrudes at the bottom surface which might allow it to contact the helix region of hNup85, as implied by the cryo-EM structure of Nup107 complex (Fig.…”

“…In the past few years, the atomic structures of several eukaryotic Nup107 components have been determined [9], such as Nup133N-terminal domain [10], the Nup133 C-terminal domain in complex with Nup107 C-terminal domain [11], the Nup85-Seh1 complex [12,13], the Sec13-Nup145C heterodimer [14], the Sec13-Nup145C-Nup84 heterotrimer [15,16], Nup120 Nterminal domain [17,18], Nup37-Nup120 [19], the Nup145C-Nup120-central triskelion [20], and the intact complex only lacking Nup133 [9]. Recently, the low-resolution structure of the human Nup107 subcomplex within the NPC scaffold was also determined by Cryo-electron microscopy (Cryo-EM) [21].…”