Molecular architecture of the transport channel of the nuclear pore complex.
The 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.
Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Sozanne R
SR
Solmaz
Radha
R
Chauhan
Günter
G
Blobel
Ivo
I
Melčák
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D051381:Rats; D016415:Sequence Alignment
D008562:Membrane Glycoproteins; D028861:Nuclear Pore Complex Proteins; C582177:Nup54 protein, rat; C518579:Nup58 protein, rat; C049312:nuclear pore protein p62