Crystal structure of the metazoan Nup62•Nup58•Nup54 nucleoporin complex

Abstract

Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport and gain transport selectivity through nucleoporin FG domains. Here, we report a structural analysis of the FG Nup62•58•54 complex, which is a crucial component of the transport system. It comprises a ≈13 nanometer-long trimerization interface with an unusual 2W3F coil, a canonical heterotrimeric coiled coil, and a kink that enforces a compact six-helix bundle. Nup54 also contains a ferredoxin-like domain. We further identified a heterotrimeric Nup93-binding module for NPC anchorage. The quaternary structure alternations in the Nup62 complex, which were previously proposed to trigger a general gating of the NPC, are incompatible with the trimer structure. We suggest that the highly elongated Nup62 complex projects barrier-forming FG repeats far into the central NPC channel, supporting a barrier that guards the entire cross section.

Perforating the nuclear boundary – how nuclear pore complexes assemble

“…Similar to the Y-complex, the Nup93 complex forms four eight-membered stacked rings resulting in 32 copies of the complex per NPC. The NPC inner ring represents the link between the pore membrane and the permeability barrier formed by FG-repeat nucleoporins: Nup93 positions the Nup62 complex, which forms a large part of the central transport channel of the NPC Chug et al, 2015). Attached to this generally symmetric NPC structure are the nuclear basket and cytoplasmic filaments, asymmetric extensions that extend into their respective compartments.…”

“…Nup53 recruits Nup155 and Nup93, which is in complex with one of the two paralogs Nup188 or Nup205 (Hawryluk-Gara et al, 2005;Theerthagiri et al, 2010;Sachdev et al, 2012;Eisenhardt et al, 2014). Nup93 also recruits, through its N-terminal coiled-coil domain, the Nup62 complex, which consists of the FG-repeatcontaining nucleoporins Nup62, Nup58 and Nup54 Chug et al, 2015), which forms a large part of the hydrophobic meshwork within the central NPC. At the same time, Nup98, another FG-repeat-containing nucleoporin that is also crucial for the exclusion and transport properties of the NPC (Laurell et al, 2011;Hulsmann et al, 2012), is integrated into the structure .…”

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

“…As proof in point, we did not obtain interactions for hsNup160 (162 kDa) and hsNup155 (155 kDa). On the other hand, three well-studied interactions were found in the human and the yeast screens: (i) the Y-complex interaction between hsNup133-Nup107 (7,40,41), (ii) the hsNup54 -Nup62 and scNup57-Nsp1 interactions in the hsNup62/scNsp1-complex (15)(16)(17)42), and (iii) the hsNup93-Nup35 interaction interolog to the scNic96 -Nup53 interaction (37,43). Similar to the hsNup133-Nup107 interaction that complemented the yeast network, additional human Nup interactions were found.…”

“…Crystallographic studies of scaffold Nups have revealed that they are largely composed of ␤-propellers and stacked ␣-helical domain elements (4,5). At least three architectural subcomplexes can be biochemically defined: the heteromeric Y-complex (6 -10), the heteromeric (yeast) Nic96/ (human) hsNup93 complex (11,12) and the trimeric Nsp1/ hsNup62 complexes (13)(14)(15)(16)(17).…”

The LINC and NPC relationship – it's complicated!

“…It remains to be determined whether any change in the diameter of the NPC is force-regulated and whether components of the LINC complex have a role in NPC dilation and constriction. It should be noted that the dilation and/or constriction of the NPC is still a matter of controversy and has been refuted by some experimental studies and observations (Stuwe et al, 2015;Chug et al, 2015). In addition, it is now well established that distinct structures (e.g.…”