Science Literature

Every cell has a nucleus equipped with gatekeepers that manage the flow of materials into and out of the nucleus. These gatekeepers are receiving much attention from researchers because of their importance to the cell and because of the perceived value placed on enhanced knowledge.

The nuclear pore is the center of so much attention because everything that goes in and out of the nucleus has to pass through. But apart from a few binding sites, "the structure is essentially a black box," Hoelz says. "And if we don't know how it looks and how it is constructed in atomic detail, then we have no way to figure out how this large transport machine works."

Core pore. A new model for the nuclear pore complex predicts that a membrane "coat" is scaffolded by two alternating pairs of upright proteins (yellow). These "fence posts" are predicted to be linked horizontally by three other yet to be discovered proteins (green). (Credit: The Rockefeller University)

A team from Rockefeller University have developed a structural model of the nuclear pore membrane and are steadily working through issues of testing and validation. In a recent paper, they report some successes:

The model proposes a cylindrical nuclear pore complex comprised of rings of alternating protein structures that zip together, providing the flexibility and space the pore needs to let pass a variety of materials in and out of the cell's nucleus. "We were very excited to find a protein that is so similar in structure to what our model predicts," Hoelz says.

Seven complex proteins are thought to provide a cylindrical coat for the pore membrane. Two pairs of proteins combine to form the rods that cross the nuclear envelope. The other three proteins are thought to join these protein pairs together to form "a picket fence of sorts". Of course, it is much more than a picket fence, because the pore is not just a structural feature, but a gatekeeper managing the flow of materials into and out of the nucleus. This higher-level functionality has yet to be understood. "The nuclear pore complex is one of the most mysterious things in cell biology. It's basically a black box," says Andre Hoelz, a research associate at The Rockefeller University

The Summary of the paper concludes: "Shared architectural and mechanistic principles with the COPII coat indicate a common evolutionary origin and support the notion that the NPC coat represents another class of membrane coats." What is of concern here is the way shared characteristics are regarded as pointers to "a common evolutionary origin". As was pointed out in a related blog a year ago, shared characteristics are also found in designed objects. By excluding the design option, the researchers are closing up possible avenues of research and artificially constraining their thinking.

This is not an abstract point to make. The nuclear pore complex is a fundamental element within all eukaryotes including humans. Malfunctioning structures can have serious consequences.

Given the central role of the nuclear pore complex in the most basic cell processes, defects in its assembly, structure and function can have lethal consequences. Its proteins have been associated with primary biliary cirrhosis, cancer, viral infections and triple A syndrome, says Erik Debler, postdoctoral fellow in the Blobel laboratory and first author of the paper. A better understanding of how the complex works could lead to treatments for these diseases.

The above quote is suggestive of irreducible complexity. If any part of the nuclear pore complex fails, the whole structure may fail to perform. There is only limited information about this at the present time, but a design perspective is open to the concept of IC and the implications if elements of the structure are faulty. If IC proves to be a valid description of any part of the nuclear pore complex, then it is pointless to pursue Darwinian mechanisms for evolving these structures because small incremental changes driven by natural selection has a very poor record for explaining the origin of such complexity.

A Fence-like Coat for the Nuclear Pore Membrane
Erik W. Debler, Yingli Ma, Hyuk-Soo Seo, Kuo-Chiang Hsia, Thomas R. Noriega, Gunter Blobel and Andre Hoelz
Molecular Cell, 26 December 2008, 32(6), 815-826 | doi: 10.1016/j.molcel.2008.12.001

Summary: We recently proposed a cylindrical coat for the nuclear pore membrane in the nuclear pore complex (NPC). This scaffold is generated by multiple copies of seven nucleoporins. Here, we report three crystal structures of the nucleoporin pair Seh1.Nup85, which is part of the coat cylinder. The Seh1.Nup85 assembly bears resemblance in its shape and dimensions to that of another nucleoporin pair, Sec13.Nup145C. Furthermore, the Seh1.Nup85 structures reveal a hinge motion that may facilitate conformational changes in the NPC during import of integral membrane proteins and/or during nucleocytoplasmic transport. We propose that Seh1.Nup85 and Sec13.Nup145C form 16 alternating, vertical rods that are horizontally linked by the three remaining nucleoporins of the coat cylinder. Shared architectural and mechanistic principles with the COPII coat indicate a common evolutionary origin and support the notion that the NPC coat represents another class of membrane coats.

See also:

New model of a nuclear pore complex is based on crystal structure of its key component, The Rockefeller University Newswire (Jan 15 2008)

New Model For Nuclear Pore Complex Backed By Structural Study, ScienceDaily (Jan. 3, 2009)

Gatekeeper for the nucleus, ARN Literature Blog (3 December 2007)