Petrovicet al., Science 376 , eabm9798 (2022) 10 June 2022 11 of 18
Fig. 6. Evolutionary conservation of the human linker-scaffold network.
(A) Domain structures of the human innerring nups. NUP93 consists of linker
(residues 1 to 173) and scaffold (residues 174 to 819) regions. (B) Schematic
summary of the linker-scaffold interactions in complexes organized around the
NUP188 and NUP205 scaffold hubs. Blacklines connecting colored bars indicate
interactions between nup regions. (C) Summary of SEC binding analysis identifying
the minimal NUP53R2region (red) sufficient for NUP93SOLbinding. +++, no effect;
++,weakeffect;+,moderateeffect;–, abolished binding. (D) Effect of each five-
alanine substitution on SUMO-NUP53NbindingtoNUP93SOL, as assessed by SEC and
indicated by colored boxes above NUP53 primary sequence. (E)Cartoon
representations of the 2.0-ÅH. sapiensapo NUP93SOL,3.4-ÅH. sapiens
NUP93SOL•NUP53R2, and 2.7-ÅC. thermophilumNic96SOL•Nup53R2(PDB ID 5HB3)
( 35 ) crystal structures and their superposition. An ~12° displacement of the
C-terminala-helical solenoid, pivoted about thehinge loop, is observed between the
apo NUP93SOLand NUP93SOL•NUP53R2structures. (F) Schematic of the human
NUP93SOLandC. thermophilumNic96SOLfold architectures. (G andH) Summary of
the effect of structure-guided mutations in (G) SUMO-NUP53Nand (H) NUP93SOL
on NUP93SOL•SUMO-NUP53Ncomplex formation, as assayed by SEC. (I to K)Magnified
views of the regions indicated with insets in (E), which compare molecular details of the
NUP53R2and Nup53R2binding sites. (L) SEC analyses of NUP93SOL•SUMO-NUP53N
complex formation and disruption by mutants. SDS–polyacrylamide gel electrophoresis
(SDS-PAGE) gel strips of peak fractions visualized by Coomassie staining.RESEARCH | STRUCTURE OF THE NUCLEAR PORE