Petrovicet al., Science 376 , eabm9798 (2022) 10 June 2022 14 of 18
Fig. 8. Linker-scaffold architecture of the human NPC inner ring.(A andB)
Composite structure generated by quantitatively docking crystal and single-
particle cryo-EM structures into an ~12-Å cryo-ET map of the intact human NPC
(EMDB ID EMD-14322) ( 47 ) viewed from (A) the cytoplasmic face and (B) the
central transport channel cross-section. Nuclear envelope and docked structures
are rendered in isosurface and cartoon representation, respectively. (C to F)
Starting from the nuclear envelope, successive layers reveal the architecture of
three inner ring spokes of the human NPC. Corresponding schematics illustrate
linker paths between binding sites on scaffold surfaces (colored circles).
NUP53RRMdomains (C) homodimerize between spokes to link cytoplasmic
peripheral with nuclear equatorial, and conversely cytoplasmic equatorial with
nuclear peripheral copies of NUP155. NUP53RRMdomains (D) link cytoplasmic
peripheral with nuclear equatorial and, conversely, cytoplasmic equatorial
with nuclear peripheral copies of NUP93SOL. NUP205 and NUP188 (E) bind to the
equatorial and peripheral NUP93R2, respectively. NUP98 connects NUP205 and
equatorial NUP155. NUP53 connects NUP205, and cross-spoke peripheral
NUP93SOL(F) CNT is recruited by NUP93R1and positioned by NUP93R2binding
to NUP188 and NUP205. (G) Close-up views of inner ring modules assembled
around NUP188 and NUP205 scaffold hubs and their superposition. Dashed lines
indicate unstructured linker nup segments and FG-repeat regions.RESEARCH | STRUCTURE OF THE NUCLEAR PORE