Molecular Architecture of the Transport Channel of the Nuclear Pore Complex

SummaryThe nuclear pore complex encloses a central channel for nucleocytoplasmic transport, which is thought to consist of three nucleoporins, Nup54, Nup58, and Nup62. However, the structure and composition of the channel are elusive. We determined the crystal structures of the interacting domains between these nucleoporins and pieced together the molecular architecture of the mammalian transport channel. Located in the channel midplane is a flexible Nup54⋅Nup58 ring that can undergo large rearrangements yielding diameter changes from ∼20 to ∼40 nm. Nup62⋅Nup54 triple helices project alternately up and down from either side of the midplane ring and form nucleoplasmic and cytoplasmic entries. The channel consists of as many as 224 copies of the three nucleoporins, amounting to a molar mass of 12.3 MDa and contributing 256 phenylalanine-glycine repeat regions. We propose that the occupancy of these repeat regions with transport receptors modulates ring diameter and transport activity.

Graphical AbstractFigure optionsDownload high-quality image (371 K)Download as PowerPoint slideHighlights
► Structure of two complexes between nucleoporins Nup54, Nup58, and Nup62
► Nup54⋅Nup58 form an expandable ring in the midplane of the transport channel
► Nup62⋅Nup54 constitute nuclear and cytoplasmic entries of the transport channel
► Transport activity may regulate channel diameter