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Biological Chemistry

New close-up views of the nuclear pore complex

Two studies bring the architecture of the cell’s mega transport machinery into better focus

by Sarah Everts
April 14, 2016 | A version of this story appeared in Volume 94, Issue 16

Structure of the nuclear pore complex.
Credit: Jan Kosinski
Structure of the nuclear pore complex, the main transport machinery in and out of the nucleus. The pore is about 1,000 Å across.

As gatekeeper of the cell’s nucleus, the nuclear pore complex (NPC) controls the shuttling of thousands of different proteins, RNA molecules, and nutrients between the nucleus and surrounding cytoplasm. Built from more than 30 types of nucleoporin proteins, and with a mass of more than 100 million daltons and a width of 1,000 Å, the NPC’s gargantuan, membrane-embedded structure has long stymied structural biologists.

Two research teams working indepen­dently have now reported the overall architecture of this mega transport machinery nearly down to the amino acid residue level.

Taking a top-down approach, a team led by Martin Beck of the European Molecular Biology Laboratory used cryo-electron microscopy, mass spectrometry, and computer modeling to determine the location of hundreds of nucleoporin proteins in the human NPC (Science 2016, DOI: 10.1126/science.aaf0643).

Meanwhile, a team led by André Hoelz of Caltech took a bottom-up approach to solve the crystal structure of fungal nucleoporin proteins containing a total some 320,000 amino acid residues (Science 2016, DOI: 10.1126/science.aaf1015). With the help of protein-protein interaction data, the team then docked those proteins into a previously published, lower resolution cryo-electron microscopy NPC structure.

Despite the different approaches and different organisms, the two teams converged on the same overall eightfold symmetrical NPC architecture. “It’s amazing that evolution maintained the same overall folds in organisms as different as humans and fungi,” Hoelz says.

The pair of papers piqued the interest of Durham University’s Martin Goldberg. “They appear to be exciting, comprehensive, and ambitious, with potentially novel insight,” Goldberg comments. But it will take careful scrutiny of the structural details—and there is a wealth of details—to capitalize on the work, he notes.

“Now that we understand the overall architecture, we need to focus on how it actually works,” Beck says. One way to do that, he adds, is by studying the peripheral proteins and protein complexes that associate with the NPC and regulate the translocation of cargo. The Hoelz team is interested in studying how viruses shut down the NPC’s transport capabilities to co-opt their host’s ribosomes in the cytoplasm to produce viral proteins without any competition from endogenous mRNA.



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