Virtuelle (Nano) Welten PDB Molecule of the Month 85:Importins

Inside your cells, the process of protein synthesis is separated into two compartments. The first half of the job, when DNA is transcribed into RNA, is performed in the nucleus. The second half is then performed outside the nucleus, when ribosomes translate the RNA to construct proteins in the cytoplasm. This separation requires a continuous traffic of molecules: new RNA molecules must be transported out of the nucleus and nuclear proteins, such as newly-synthesized histones or polymerases, must be transported back into the nucleus. Huge tube-shaped nuclear pores act as the highway connecting the nucleus and the cytoplasm, and importins and exportins (collectively known as karyopherins) ferry molecules back and forth through the pore.

Special Delivery

Importins transport thousands of different proteins into the nucleus to perform the many tasks of storing, reading, and repairing the genome. However, it would be far too costly to design a special importin to carry each one inside. Instead, many nuclear proteins are built with a special tag—a short sequence called the nuclear localization signal—that tells the transport machinery to carry the protein into the nucleus. Importins recognize this signal, bind to the protein, and transport it through the nuclear pore.

The Import Business

The importin complex shown here (built from three separate PDB entries) transports proteins with nuclear localization signals. At the top in blue is importin-beta (PDB entry 1qgk). It is the engine of the complex, recognizing nuclear pores and moving through them. It wraps around the end of importin-alpha, shown at the center in green (PDB entry 1ee5). Importin-alpha is an adapter molecule that connects importin-beta with the cargo. In this picture, the cargo is nucleoplasmin, shown at the bottom in yellow (PDB entry 1k5j), a chaperone protein that is important in nucleosome assembly. Notice how the extended nuclear localization signal of this cargo is gripped by importin-alpha.

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