A Fence-like Coat for the Nuclear Pore Membrane

Abstract

We recently proposed a cylindrical coat for the nuclear pore membrane in the nuclear pore complex (NPC). This scaffold is generated by multiple copies of seven nucleoporins. Here, we report three crystal structures of the nucleoporin pair Seh1*Nup85, which is part of the coat cylinder. The Seh1*Nup85 assembly bears resemblance in its shape and dimensions to that of another nucleoporin pair, Sec13*Nup145C. Furthermore, the Seh1*Nup85 structures reveal a hinge motion that may facilitate conformational changes in the NPC during import of integral membrane proteins and/or during nucleocytoplasmic transport. We propose that Seh1*Nup85 and Sec13*Nup145C form 16 alternating, vertical rods that are horizontally linked by the three remaining nucleoporins of the coat cylinder. Shared architectural and mechanistic principles with the COPII coat indicate a common evolutionary origin and support the notion that the NPC coat represents another class of membrane coats.

Integrative structure and functional anatomy of a nuclear pore complex

“…Our data invalidate this assumption (Fig. 1; Supplementary Table 2A; Supplementary Results and Discussion) as well as an earlier “fencepost” model 41 . In summary, there is no single universal NPC structure; instead, similar structural elements are used in somewhat different arrangements to generate many lineage-specific adaptations.…”

Structure of a trimeric nucleoporin complex reveals alternate oligomerization states

“…The compact U-shaped ␣-helical solenoid domain of the Nup84 NTD (Fig. 2) resembles the topology of the ␣-helical solenoid domains of Nup145C and Nup85, two other nucleoporins of the heptameric complex (26,27). The majority of the Nup84 NTD ␣ helices are arranged in an antiparallel manner, with helices ␣A-E forming the descending arm of the U, while helices ␣L-Q represent the ascending arm.…”

“…Interestingly, Sec13 is shared between the NPC and the COPII cage, where it forms the outer coat layer in complex with Sec31 (29)(30)(31)(32)(33). Remarkably, the heptamer shares architectural principles with the clathrin triskelion (23), and the molecular model of the COPII cage includes an elongated, curved Sec13⅐Sec31 hetero-octamer that possesses similar architectural features to the Sec13⅐Nup145C and Seh1⅐Nup85 hetero-octamers, which indicates a common evolutionary origin and suggests a physiological relevance of the hetero-octameric assemblies (26)(27)(28)(29)33).…”

“…We hypothesized that the elongated, curved Sec13⅐Nup145C and Seh1⅐Nup85 hetero-octamers form vertical rods in a fencelike coat for the nuclear pore membrane (26,27). Most recently, structural and functional analyses of Nup120 identified an interaction with Nup133 and confirmed its physiological relevance.…”

“…This analysis identified specific hinge regions at which the heptamer shows great flexibility, and allowed for the docking of atomic structures of its components into the EM envelope: the Nup133 N-terminal domain (24), Nup107⅐Nup133 (Nup107 is the human homolog of Nup84) (25), Sec13⅐Nup145C (26), and Seh1⅐Nup85 (27).…”