Getting to the core of nuclear pores

Spanning the nuclear membrane in eukaryotic cells, nuclear pore complexes (NPCs) are the primary gateways through which messenger RNA and other macromolecules travel between the nucleus and the surrounding cytoplasm. The NPC is nature’s largest protein complex, comprising some 10 million atoms and assembled from multiple copies of about 30 distinct proteins known as nucleoporins. Whereas the nucleoporins that extend into the cytoplasm and nucleus differ, those lining the pore itself form a symmetric sandwich, as shown here, with two outer rings (orange and blue) and an inner ring (yellow and green) that line the pore in the nuclear membrane (gray). The core scaffoldings in eukaryotes from amoebas to zebras have much in common. Yet the exact structure has been elusive.

Two groups—one led by André Hoelz at Caltech and one by Martin Beck at the European Molecular Biology Laboratory (EMBL)—now present detailed maps of the NPC. With chromatography and x-ray crystallography, Hoelz and colleagues systematically mapped the biochemical and structural interactions among fungus nucleoporins. Armed with those data, they were able to assemble the interlocking pieces to re-create the moderate-resolution (23 Å) human NPC structure that Beck’s group obtained last year through cryo-electron tomography. Meanwhile, Beck and coworkers used molecular modeling combined with mass spectrometry and refined tomography to obtain a composite structure of the inner ring of the human NPC. The new NPC architectures lay the foundation for understanding the NPC’s role in aging, cancer, and other diseases. (D. H. Lin et al., Science 352, 308, 2016; J. Kosinski et al., Science 352, 363, 2016. Image by Jan Kosinski, EMBL.)

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