Saccharomyces cerevisiae
An Architectural Guide to the Nuclear Pore Complex
Posted on by Dr. Francis Collins
Credit: The Rockefeller University, New York
Sixty years ago, folk singer Pete Seeger recorded a song about helping those in need. The song starts like this: “Oh, had I a golden thread/And a needle so fine/I’d weave a magic strand/Of rainbow design.” In this brief animation, it seems like a golden thread and a needle are fast at work. But this rainbow design helps to answer a longstanding need for cell biologists: a comprehensive model of the thousands of pores embedded in the double-membrane barrier, or nuclear envelope, that divides the nucleus and its DNA from the rest of the cell.
These channels, called nuclear pore complexes (NPCs), are essential for life, tightly controlling which large macromolecules get in or out of the nucleus. Such activities include allowing vital proteins to enter the nucleus, blocking out harmful viruses, and shuttling messenger RNAs from the nucleus to the cytoplasm, where they are translated into proteins.
This computer simulation starts with an overhead view of the fully formed NPC structure. From this angle, the pore membrane (gray) appears to be at the base and is embroidered in four rings that are the channel’s main architectural support beams. There’s the cytoplasmic outer ring (yellow), the inner rings (purple, blue), the membrane ring (brown), and the nucleoplasmic outer ring (yellow). Each color represents different protein complexes, not rings per se, and the hole in the middle is the central channel through which molecules are transported. Filling the hole is a selective gating mechanism made of disordered protein (anchored to green) that helps to get the right molecules in and out.
Creative Minds: Of Arsenic and Misfolded Proteins
Posted on by Dr. Francis Collins
John Hanna
Taking out the trash is a must in every household. Inside our cells, it’s also essential because if defective proteins are not properly disposed of, they can accumulate and make a mess of the cell’s inner workings, leading to health problems.
John Hanna, a physician-scientist at Brigham and Women’s Hospital, Boston, is on a quest to study the cell’s trash disposal system in greater detail. In particular, this 2014 NIH Director’s Early Independence awardee wants to learn more about how cells identify proteins that need to be discarded, how such proteins are steered towards the molecular garbage can, and how, when the process breaks down, neurodegenerative conditions, cancers, and other diseases can arise.
That’s a complex challenge, so Hanna will start by zeroing in on one particular component of cellular waste management—the component that clears out proteins damaged by arsenic. Although arsenic is notorious for being the poison of choice in countless true crime shows and mystery novels, this semi-metallic element is found naturally in soil, water, air, and some foods.
