Post details: Gatekeeper for the nucleus

12/03/07

Permalinkby 12:00:32 pm, Categories: Literature - Articles, 921 words   English (UK)

Gatekeeper for the nucleus

Jigsaw buffs will enjoy the "Pore Puzzle" essay by Aitchison and Wozniak cited below. How do we approach the challenge of putting together a 1,000 piece picture?

"We solve the puzzle by considering each piece and ruling out those that don't fit physical restraints, such as colour patterns, the overall shape of the picture and the potential for interlocking. This is the basic premise for the multidisciplinary approach taken by Alber et al. to solve the structure of a large molecular machine, the yeast nuclear pore complex. But, in their case, the pieces were proteins, the various restraints were of a biochemical and morphological nature, and computers explored the placement of each protein into a single ensemble solution."

Within the cell, many thousands of different molecules are produced to accomplish the various tasks that need to be done. The nuclear envelope sets up a special environment within the cell. The enabling mechanism is the nuclear pore complex (NPC) which regulates the movement of molecules into and out of the nucleus. It is the architecture of this complex that has now been published for the first time. By all accounts, the authors' achievement is remarkable.
It is not surprising that striking patterns emerge in the detailed structure of the complex. However, the authors use this to suggest that their work provides pointers to an evolutionary origin from an ancestral structure. The relevant paragraph comes in their concluding remarks:

"Although the NPC is a complex structure, our analysis reveals underlying simplicities in its architecture. At its heart, the NPC contains a highly connected scaffold that attaches to and coats the curved pore membrane. The fold composition of the nucleoporins forming the scaffold is remarkably simple, consisting of only two different domain folds, the configurations of which resemble those found in vesicle-coating complexes - to which the NPC may therefore be evolutionarily related. [. . .] thus, the NPC is another example of how a complicated structure can evolve from the duplication, divergence and elaboration of simple ancestral modules."

This paragraph reveals one of the fundamental premises of Darwinism: as we come to understand the inner workings of organisms, things are supposed to get simpler. This simplicity then allows step-by-step transformation. Darwinists look for underlying simplicity - and let us know whenever they find it! Simplicity, however, can also be a design feature - particularly when NPCs have to be manufactured quickly by the cell every time it divides. Everyone involved with new product development knows that "simplification" is one of the keywords describing their (intelligent) activities. Having said this, it should be noted that the authors are referring only to structural simplification: the arrangement of the component parts. The real complexity of the NPC is to be found in the regulation work it has to do. This is where the information content of the NPC goes off scale! A biologist commented on this as follows:
The claim of underlying simplicity "ignores the chaperones and gatekeepers that are involved in the transport process. It ignores that there is one way and two way trafficking through the pore. Just the idea that the pore can discriminate between different nucleic acids, (which includes many different size heterogeneous RNAs, mRNA, primary transcript RNA and DNA), which are very similar suggests a certain basal level of complexity. In light of this, this pore in my estimation could be one of the most complex in the cell!"

The authors can be credited with some excellent science, but they have spoilt it by some parting comments about the evolution of the NPC that can only be described as speculative. Far better is to propose testable hypotheses. If the Darwinian approach is valid, further research will reveal further evidences of underlying simplicity relating to the information processing capabilities of the structure. Conversely, if further research reinforces complexity, the Darwinian paradigm should be discarded as unproductive. There is already enough evidence in the NPC to infer design, and the "underlying simplicity" of the structure communicates "evolution" only to those who are predisposed to receive it.

The molecular architecture of the nuclear pore complex
Frank Alber, Svetlana Dokudovskaya, Liesbeth M. Veenhoff, Wenzhu Zhang, Julia Kipper, Damien Devos, Adisetyantari Suprapto, Orit Karni-Schmidt, Rosemary Williams, Brian T. Chait, Andrej Sali & Michael P. Rout.
Nature 450, 695-701 (29 November 2007) | doi:10.1038/nature06405

Abstract: Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC's 456 constituent proteins (see the accompanying paper). Our structure reveals that half of the NPC is made up of a core scaffold, which is structurally analogous to vesicle-coating complexes. This scaffold forms an interlaced network that coats the entire curved surface of the nuclear envelope membrane within which the NPC is embedded. The selective barrier for transport is formed by large numbers of proteins with disordered regions that line the inner face of the scaffold. The NPC consists of only a few structural modules that resemble each other in terms of the configuration of their homologous constituents, the most striking of these being a 16-fold repetition of 'columns'. These findings provide clues to the evolutionary origins of the NPC.

Pore puzzle
John D. Aitchison & Richard W. Wozniak
Nature 450, 621 (29 November 2007) | doi:10.1038/450621a

Abstract: Where would you start in trying to work out the structure of a macromolecular machine consisting of 456 proteins? Taking a combined experimental and computational approach is one answer.

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