Yasemin Saplakoglu writes:

At the dawn of complex life, evolution created a container for DNA, its most treasured item. A few billion years later, 20th-century microscopists looked at this container — the nucleus — up close and saw that it was covered in tiny openings. At the time, they didn’t know what to make of these structures, but as microscopy improved, something grand came into focus: what we now call “nuclear pore complexes,” some of the largest and most marvelous molecular machines ever formed.

Every nuclear pore complex is constructed from hundreds of proteins, of around 30 different types. From the front, it looks like an eight-petaled flower; from the side, like a flying saucer. Its center opening spills over with spaghetti-like proteins tethered to the inner walls of the complex.

“It’s a thing of enormous beauty,” said Brian Chait, a chemical biologist at Rockefeller University. “It’s marvelous. It’s a wonder. … It’s phenomenal.”

This machine has a vital job: directing molecular traffic into and out of the nucleus. More than an open door, the protein complex recognizes different molecules as they approach — and lets only some through. “The nuclear pore complex is ultimately the gatekeeper for the nucleus,” said Roderick Lim, a biophysicist at the University of Basel in Switzerland. “Everything that has to get in and out of the nucleus has to go through these pores.”

Nearly every eukaryotic cell has a nucleus punctured with nuclear pore complexes, and the main components of the complex are incredibly conserved across species, from single-celled yeasts to multicellular humans. Evolution “came up with that thing one time and got stuck with it,” said André Hoelz, a structural cell biologist at the California Institute of Technology.

A single mammalian nucleus can contain thousands of them. Every second, each nuclear pore lets hundreds to thousands of molecules of all shapes and sizes pass through so that they can travel to their destinations to make proteins, regulate genes, and generally help the cell function. Some large molecules are carried through the channel by proteins, while small ones diffuse across on their own. And while some effortlessly glide through, to others it is an impenetrable barrier.

How this gate works with such selectivity is a mystery. Over decades, biologists have worked out what most of the static parts of the machine look like. But its center is restless, endlessly moving and morphing, which makes it difficult for even the best methods to visualize. [Continue reading…]