Internal Beauty: the Nuclear Pore Complex
Like a 3-D puzzle solved in 15 minutes, the
nuclear envelope is a wonder to behold
by Margaret Helder, PhD
Imagine that you are a jigsaw puzzle fan. There really are such people! Imagine furthermore that you have been given a special challenge, a five-hundred-piece, three-dimensional puzzle made up of thirty different shapes. How long would it take you to solve that puzzle and reproduce the designated architecture? Years maybe? Actually, you are smarter than you think. The cells in your body solve this challenge in 15 minutes maximum! How do they do it? Nobody knows, but the story is interesting.
It so happens that every cell in your body comes equipped with a nucleus which contains the information necessary to direct the life activities of that cell. Inside the nucleus, information is downloaded from the DNA into copies (RNA) which must proceed out to the surrounding cell material (cytoplasm) in order to produce the proteins needed to provide structure and operating capabilities for the cell. Any large molecules which need to enter or exit the nucleus, must pass through special gates or pores in the nuclear envelope. There are thousands of such pores in the nuclear envelope. Special molecular machines, by far the largest in the living cell, form special gateways called nuclear pore complexes. These each consist of 500 protein molecules which come in 30 different shapes and sizes. So now you know the identity of the puzzle challenge already noted.
Considering that the nuclear envelope is so important to protect the nucleus, it seems amazing that when the cell is about to divide, it eliminates the nuclear envelope! The nucleus thus divides out in the open cell. However, as the process of division ends, the cell hurriedly forms a new nuclear envelope around each of the two daughter nuclei preparatory to forming two new daughter cells. So how do we know what each nuclear pore complex (NPC) is like and how they function? Read on to find out.
In November 2007, studies on the architecture of the NPC (nuclear pore complex) were selected as the cover story for an issue of the journal Nature1. From electron microscopy, scientists knew what the basic appearance of the NPC was, but they had no idea how the component proteins fit together. By means of X-ray crystallography and other studies, they obtained some idea of the shapes of the component proteins. They also figured out how many copies of each individual protein there were in the complex. Now it was time to figure out how they all fit together. A computer ran repeated attempts to fit all the components into a three-dimensional array that fit the overall appearance. In the end, the scientists were satisfied that a computer had more or less identified a best fit solution to the challenge. Think of the information manipulating abilities of the computer that allowed it to solve the best fit of the component parts. The computer solved the jigsaw puzzle challenge for the scientists. But how does the cell solve this puzzle in 15 minutes or less and why does it need such speed?
Nuclear envelope with NPCs (Illustra Media)
The nuclear envelope quickly forms around the nucleus to protect the genetic information inside. At the same time, about 4000-5000 gaps in the envelope are filled with the nuclear pore complex machinery. Somehow metabolic processes direct the 500 protein molecules in each NPC to assume exactly the correct architecture. They will need to be perfect so that appropriate large molecules can enter or exit the nucleus. There is one extra frill however. As the nucleus grows larger after cell division, more nuclear pores are needed. The fascinating thing is that in this case, the NPCs form by a different process which takes longer (about an hour to complete), but the composition and function of the new NPCs are the same as the ones that formed earlier.2
The macromolecular machine which forms the nuclear pore complex consists of two doughnut-like structures stacked together, one facing the nuclear interior, and the other facing the cytoplasmic exterior cell material. Inside the channel-proper, lie flexible tangled filaments with no fixed shape. It is these filaments which control whether cargo gets past them into or out of the nucleus.3 But the situation is not exactly simple in that plugged pore region.
Let us focus our attention inside the nucleus. Proteins (which came into the nucleus from the cytoplasm) are required to expedite the copying of information from DNA into RNA. Spliceosomes (more proteins) then chop out certain unneeded sections of the RNA molecule. We now have a strand of messenger RNA (mRNA) which will (once it has emerged into the cytoplasm) direct the manufacture of a specific protein needed by the cell. But the mRNA can’t get out of the nucleus (yet). Proteins must form a cap on the front end of the chain and a long tail of adenosine monophosphate (like adenosine triphosphate or ATP, only lacking two phosphate groups) attaches to the back end. The tail stabilizes the long chain of nucleotides. This complex is now called mRNP (ribonucleoprotein complex). Finally, a transcription-export complex connects to the mRNP cargo. The filaments in the channel-proper of the NPC now recognize the cargo, and carry it across the nuclear envelope out into the cytoplasm.4
The living cell is evidently a masterpiece of precision and mind-boggling complexity. The nuclear envelope (a double membrane around the nucleus) is just a very small component of the cell. Nevertheless, this envelope performs an essential function, to protect the integrity of the genetic information in the nucleus and the information coming out of the nucleus into the surrounding cell material (cytoplasm). It is here in the cytoplasm that the information coming from the nucleus is turned into reality. The cell will die, or lose vigor if false information is allowed to emerge from the nucleus. It is the role of the NPC to prevent this, as much as possible, from happening. Thus many steps are required in the nucleus before a piece of suitably packaged mRNA (now called mRNP) can be recognized by a transport export factor which expedites the cargo’s attaching to the channel filaments which then carry the cargo safely through to the opposite side.5
Even more amazing to people who understand three-dimensional architectures, is how the cell manages to juggle 500 individual proteins (in 30 different shapes), precisely arranging them within minutes into a beautiful functional structure, the NPC. It is like building a house within minutes instead of weeks or months.
One process used to form the NPC would be dramatic enough. However, the cell most unexpectedly manages to utilize two fundamentally different processes which display “distinct kinetic, molecular and structural features”6. Nevertheless, the cell still builds exactly the same protein complex as by the first process. If the final arrangement from the second process resulted in a different arrangement from the first process, we might suppose that it didn’t really matter what the arrangement of proteins was in the NPC. But that is not the case. To achieve the same structure by two routes when there are so many component pieces which could potentially be placed incorrectly, obviously makes the resulting architecture most improbable if only chance processes were involved.
The choices and skill required to build the NPC complex even once, are astounding, but to build it a second time while manipulating the pieces in a different order, demonstrates that supernatural intelligence is required. We know that God, the Creator, in addition to everything else, is artistic and loves beauty as well designs that function. The NPC fulfills all these criteria. All praise to God, the Creator!
References :
1. Frank Alber et al. 2007. Determining the architectures of macromolecular assemblies. Nature 450 Nov. 29 pp. 683-694. And Frank Alber et al. 2007. The molecular architecture of the nuclear pore complex. Nature 450 Nov. 29 pp. 695-701.
2. Shotaro Otsuka et al. 2023. A quantitative map of nuclear pore assembly reveals two distinct mechanisms. Nature 613 January 19 pp. 575-581. “Our data revealed that the two NPC assembly pathways are markedly different.” p. 579
3. Miao Yu et al. 2023. Visualizing the disordered nuclear transport machinery in situ. Nature 617 May 4 pp. 162-169.
4. Belen Pacheco-Fiallos et al. 2023. mRNA recognition and packaging by the human transcription-export complex. Nature 616 April 27 pp. 828-835. And Otsuka et al. 2023.
5. Belen Pacheco-Fiallos et al. 2023. and Frank Alber et al. Determining the architectures of macromolecular assemblies. 2007. “Filling this tube and projecting into both the cytoplasmic and nuclear sides are flexible filamentous domains from proteins termed FG (phenylalanine-glycine) repeat nucleoporins; these domains form the docking sites for transport factors that carry macromolecular cargoes through the NPC” p. 683.
6. Shotaro Otsuka et al. 2023. p. 575.
Margaret Helder completed her education with a Ph.D. in Botany from Western University in London, Ontario (Canada). She was hired as Assistant Professor in Biosciences at Brock University in St. Catharines, Ontario. Coming to Alberta in 1977, Dr Helder was an expert witness for the State of Arkansas, December 1981, during the creation/evolution ‘balanced treatment’ trial. She served as member of the editorial board of Occasional Papers of the Baraminology Study Group in 2001. She also lectured once or twice a year (upon invitation) in scheduled classes at University of Alberta (St. Joseph’s College) from 1998-2012. Her technical publications include articles in the Canadian Journal of Botany, chapter 19 in Recent Advances in Aquatic Mycology (E. B. Gareth Jones. Editor. 1976), and most recently she authored No Christian Silence on Science (2016) which promotes critical evaluation of scientific claims. She is married to John Helder and they have six adult children.