Journal Article

The molecular architecture of the nuclear pore complex

Karni-Schmidt, Orit, Rout, Michael P., Kipper, Julia, Williams, Rosemary, Dokudovskaya, Svetlana, Zhang, Wenzhu, Alber, Frank, Devos, Damien, Suprapto, Adisetyantari, Chait, Brian T., Veenhoff, Liesbeth M., Sali, Andrej

2007

Overview

Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC’s 456 constituent proteins (see the accompanying paper). Our structure reveals that half of the NPC is made up of a core scaffold, which is structurally analogous to vesicle-coating complexes. This scaffold forms an interlaced network that coats the entire curved surface of the nuclear envelope membrane within which the NPC is embedded. The selective barrier for transport is formed by large numbers of proteins with disordered regions that line the inner face of the scaffold. The NPC consists of only a few structural modules that resemble each other in terms of the configuration of their homologous constituents, the most striking of these being a 16-fold repetition of ‘columns’. These findings provide clues to the evolutionary origins of the NPC. Gatekeeper for the Nucleus The nuclear pore complex plays a crucial role in the cell, as gatekeeper for traffic between the cytoplasm and the interior of the nucleus. It is a large supramolecular complex made up of multiple copies of about 30 different proteins — 456 protein molecules in all. Cell biologists would love to know how each of the pore molecules are placed, but so far this has eluded conventional structural studies. Now, a new proteomics-based technique has provided a detailed view of the architecture of the yeast nuclear pore complex. Half of the complex is made of a core scaffold forming a network coating the surface of the nuclear envelope membrane within which the complex is embedded. The selective transport barrier is formed by the many proteins lining the inner face of the scaffold. Despite its size, there are only a few structural modules in the complex; this underlying simplicity provides possible pointers to an evolutionary origin from a 'primordial' nuclear pore complex. In the cover graphic, the 100-nm diameter pores are shown in the silver-grey nuclear envelope.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Active Transport, Cell Nucleus / Binding Sites / Cell Nucleus - metabolism / Cellular biology / Cytoplasm - metabolism / Evolution, Molecular / Humanities and Social Sciences / Macromolecular Substances - chemistry / Macromolecular Substances - metabolism / Molecular biology / Molecular structure / multidisciplinary / Nuclear Envelope - metabolism / Nuclear Pore - chemistry / Nuclear Pore - metabolism / Nuclear Pore - ultrastructure / Nuclear Pore Complex Proteins - analysis / Nuclear Pore Complex Proteins - chemistry / Nuclear Pore Complex Proteins - metabolism / Nuclear Pore Complex Proteins - ultrastructure / Protein Conformation / Proteins / Saccharomyces cerevisiae - chemistry / Saccharomyces cerevisiae - cytology / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae - ultrastructure / Saccharomyces cerevisiae Proteins - analysis / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - metabolism / Saccharomyces cerevisiae Proteins - ultrastructure / Science / Yeasts