Feature

Giant, intricate structures

Laurel Oldach
Dec. 6, 2022

Structural biologists increasingly are able to determine in intricate detail the baroque structures of large protein complexes with important roles in the cell. This year, that was especially clear with the nuclear pore complex, or NPC.

A special issue of the journal Science featured five papers that tackled the NPC from various angles and in different species, in what senior editor Di Jiang called “a triumph of experimental structural biology.”

The nuclear pore complex includes four rings built from symmetrically repeated patterns of about 30 nucleoporin proteins. The complex is enormous, comprising roughly 1,000 protein subunits in total. This structure controls access to the nucleus, selectively allowing cargo such as signaling proteins and mRNAs in or out of the nucleus. It also, researchers recently have shown, can dilate and contract, changing the diameter of the central channel by almost 50%.

Much like working a 3-D puzzle, researchers solved the structure of the nuclear pore complex by fitting the known subunit structures into a vague outline of the whole.
Much like working a 3D puzzle, researchers solved the structure of the nuclear pore complex by fitting the known subunit structures into a vague outline of the whole.

Building on advances in the structure of the human NPC’s core rings published in 2016, three research teams tackled the cytoplasmic face of the NPC in human, frog and yeast cells. Each combined knowledge about the structures of individual nucleoporins and small groups of proteins, determined through biochemistry, crystallography or protein structure prediction, with larger-scale but blurrier models of the NPC as a whole derived from cryo-electron microscopy or tomography. Hao Wu, a structural biologist at Harvard Medical School who led one of the research teams, compared the workflow to solving a jigsaw puzzle by fitting the smaller subunits into the larger complex’s outlines.

One of the three teams that studied the cytoplasmic face, led by Andre Hoelz at Caltech, also published a second paper investigating linker nucleoporins buried deep in the core in the nuclear envelope. The team probed the combination of flexible and tight crosslinks that allow the inner channel of the NPC to dilate but also constrain its expansion.

A fourth team, from Martin Beck’s lab at the Max Planck Institute of Biophysics, published an integrative structural analysis that took on the whole NPC. The researchers used cryo-electron tomography to develop a model of the whole complex in its constricted and dilated conformations along with structural prediction to figure out multiple possible conformations of uncharacterized scaffold nucleoporins. Like the researchers studying the cytoplasmic face of the NPC, the team then fit these subunits into a larger model — this one equipped for molecular dynamics simulations that enabled them to predict how the pore complex as a whole might move.

The work has important implications for how the cell builds one of its most complex machines and for understanding how various molecules pass in and out of the nucleus. It also has inspired researchers to use similar techniques to tackle other large complexes.

“We are now looking at other highly complex structures,” Wu said.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Laurel Oldach

Laurel Oldach is a former science writer for the ASBMB.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Opinions

Opinions highlights or most popular articles

Talking about maximizing access
President's Message

Talking about maximizing access

Feb. 1, 2023

Ann Stock, president of the ASBMB, talks to Sonia Flores about the society’s Maximizing Access Committee, better known as the MAC.

What to read and watch during Black History Month
Observance

What to read and watch during Black History Month

Feb. 1, 2023

The ASBMB Maximizing Access Committee shares its picks.

Common psychotropic meds disrupt cholesterol synthesis in brain
Journal News

Common psychotropic meds disrupt cholesterol synthesis in brain

Jan. 31, 2023

Mouse study explains why adults sometimes get misdiagnosed with rare syndrome that affects babies.

Science meets soccer: It’s all about passion
Essay

Science meets soccer: It’s all about passion

Jan. 23, 2023

"As in sports, success in science is not only about intrinsic talent or natural abilities. It requires genuine commitment, eagerness to learn, discipline, teamwork — and truthfully, sometimes a bit of luck."

Equal benefits for postdocs
Jobs

Equal benefits for postdocs

Jan. 17, 2023

Postdocs on federal fellowships should receive equal benefits as peers, write Mallory R. Smith and Thomas P. Kimbis.

China now publishes more high-quality science than any other nation
Essay

China now publishes more high-quality science than any other nation

Jan. 15, 2023

Thanks to investment and a growing, capable workforce, the country’s scientific output has increased steadily and become more novel and creative.