Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex

Abstract

ABSTRACTThe nuclear pore complex (NPC) is a highly modular assembly of 34 distinct nucleoporins (Nups), to form a versatile transport channel between the nucleus and cytoplasm. Among them, Nup62 is known as an essential component for nuclear transport while, Nup93 for the proper nuclear envelope assembly. These Nups constitute various NPC subcomplexes: such as central transport channel (CTC), cytoplasmic ring (CR) and inner ring (IR). However, how they play their role in the NPC assembly and transport activity is not clear. Here we delineated the interacting regions, conducted biochemical reconstitution and structural characterization of the mammalian CR complex to reveal its intrinsic dynamic behaviour and a distinct ‘4’ shaped architecture resembling the CTC complex. Our data demonstrate that Nup62 coiled-coil domain is critical to form both Nup62•Nup88 and Nup62•Nup88•Nup214 heterotrimers and both can bind to the Nup93. We therefore propose that Nup93 act as a ‘sensor’ to bind to Nup62 shared heterotrimers including Nup62•Nup54 heterotrimer of the CTC, which was not shown previously as an interacting partner. Altogether, our study establishes that the Nup62 via its coiled-coil domain is central to form compositionally distinct yet structurally similar heterotrimers, and the Nup93 anchors these diverse heterotrimers by recognizing them non-selectively.