Figure 12–8 The arrangement of NPCs in the nuclear envelope. (a) in a vertebrate npC, nucleoporins are arranged with striking eightfold rotational symmetry. in addition, immunoelectron microscopic studies show that the proteins that make up the central portion of the npC are oriented symmetrically across the nuclear envelope, so that the nuclear and cytosolic sides look identical. The eightfold rotational and twofold transverse symmetry explains how such a huge structure can be formed from only about 30 different proteins: many of the nucleoporins are present in 8, 16, or 32 copies. Based on their approximate localization in the central portion of the npC, nucleoporins can be classified into (1) transmembrane ring proteins that span the nuclear envelope and anchor the npC to the envelope; (2) scaffold nucleoporins that form layered ring structures. some scaffold nucleoporins are membrane-bending proteins that stabilize the sharp membrane curvature where the nuclear envelope is penetrated; and (3) channel nucleoporins that line a central pore. in addition to folded domains that anchor the proteins in specific places, many channel nucleoporins contain extensive unstructured regions, where the polypeptide chains are intrinsically disordered. The central pore is filled with a tangled mesh of these disordered domains that blocks the passive diffusion of large macromolecules. The disordered regions contain a large number of phenylalanine-glycine (fG) repeats. fibrils protrude from both the cytosolic and the nuclear sides of the npC. By contrast to the twofold transverse symmetry of the npC core, the fibrils facing the cytosol and nucleus are different: on the nuclear side, the fibrils converge at their distal end to form a basketlike structure. The precise arrangement of individual nucleoporins in the assembled npC is still a matter of intense debate, because atomic resolution analyses have been hindered by the sheer size and flexible nature of the npC, and by difficulties in purifying sufficient amounts of homogeneous material. a combination of electron microscopy, computational analyses, and crystal structures of nucleoporin subcomplexes has been used to develop the current models of the npC architecture. (B) a scanning electron micrograph of the nuclear side of the nuclear envelope of an oocyte (see also figure 9–52). (C) an electron micrograph showing a side view of two npCs (brackets); note that the inner and outer nuclear membranes are continuous at the edges of the pore. (D) an electron micrograph showing face-on views of negatively stained npCs. The membrane has been removed by detergent extraction. note that some of the npCs contain material in their center, which is thought to be trapped macromolecules in transit through these npCs. (a, adapted from a. hoelz, e.W. Debler and G. Blobel, Annu. Rev. Biochem. 80:613– 643, 2011. With permission from annual reviews; B, from m.W. Goldberg and T.D. allen, J. Cell Biol. 119:1429–1440, 1992. With permission from The rockefeller University press; C, courtesy of Werner franke and Ulrich scheer; D, courtesy of ron milligan.) through a large, expandable, aqueous pore, rather than through a protein transporter spanning one or more lipid bilayers. For this reason, fully folded nuclear proteins can be transported into the nucleus through an NPC, and newly formed ribosomal subunits are transported out of the nucleus as an assembled particle. By contrast, proteins have to be extensively unfolded to be transported into most other organelles, as we discuss later.
nuclear import receptors Bind to Both nuclear localization signals and npC proteins