Ring cycle for dilating and constricting the nuclear pore - PubMed (original) (raw)

Ring cycle for dilating and constricting the nuclear pore. (A–D) Summary of modules of determined X-ray structures of segments derived from channel nucleoporins Nup54, Nup58, and Nup62 (Fig. 1). (A) Nup54•Nup58 dodecamer consisting of eight Nup54 (blue) and four Nup58 (red) protomers; note the “bent” and “straight” conformers of the Nup54 protomer (12). (B) Nup58 homotetramer; each protomer consists of a helical hairpin (11). (C) Nup54 homotetramer with two distinct conformers of the Nup54 protomer (

Fig. S3 A and B

). (D) Nup62•Nup54 triple helix (12), with two protomers of Nup62 in gray and one protomer of Nup54 in blue. For visual simplification, the structural elements of the modules are schematically modified in E–J. (E and F) We propose that eight of each of the modules shown in A–C form a ring, representing dilated and constricted states. (E) In the dilated state, eight Nup54•Nup58 dodecamers form a midplane ring, the diameter of which is flexible in the range between 40–50 nm as a result of intramodular sliding (12). (F) For constricting the pore, the 96 constituent protomers of the dilated midplane ring resolve into three homooligomeric rings of 32 protomers each; because of its twofold symmetry, the Nup58 ring is placed in midplane (11), whereas the two Nup54 rings are tentatively placed below and above (F) or tucked within the Nup58 ring (

Fig. S5

). The three homooligomeric rings, stacked in midplane, display a diameter in the 10- to 20-nm range (

Figs. S4

and

S5

). (G and H) Finger attachments to the dilated midplane ring (G) and to the two Nup54 rings in the constricted state (H): A flexible linker region of Nup54, indicated as blue transparent tube, continues into a Nup62•Nup54 triple helix (D), simplified to a vertically oriented, blue and gray cylinder and termed finger; note the presence of a total of 64 fingers, 32 each on the nucleoplasmic and cytoplasmic sides; cycling from a dilated to a constricted state (G to H) increases crowding of fingers. (I and J) Schematic tracing of full-length channel nups (Fig. 1) in a vertical slice across the dilated (I) and constricted (J) state; distinct nup regions are labeled (see text) and indicated by arrows; color-coded N depicts the N terminus in one each of three channel nups; an “unsaturated valence” of Nup62 (only one of two is indicated) and of Nup58 for a yet-to-be-identified segment of another nup, is indicated by a yellow and a green bar, respectively (Fig. 1); note location of the two FG repeats of Nup58: C-terminal FG repeat projects to the center of the midplane ring, whereas the N-terminal FG repeat projects away from the pore, suggesting that it may bind to a solenoid nucleoporin in the surrounding of the central transport channel. Tracing the path of all three channel nucleoporins, Nup58, Nup54, Nup62, through a single transport channel of the NPC, in copies of 32:64:128 (12), indicates that the three channel nups not only line the channel but also anchor it to the surrounding matrix of nups. Anchorage would be accomplished by 128 binding sites emanating from Nup62, at the base of the fingers, and by 32 binding sites from the Nup58 midplane ring.