On several previous occasions on this blog I've discussed proteins that undergo significant changes in structure without drastic changes in their primary sequence or solution conditions. In some cases, a few mutations can take a protein to a novel fold, as with Philip Bryan's protein G work. In others, closely related sequences within a whole family populate different kinds of folds, as Matt Cordes illustrated for the case of Cro proteins. In addition, there are some cases such as lymphotactin, where interconversion between two very different structures takes place at equilibrium, as illustrated by Brian Volkman's research. Each time stories like this come up I have mentioned that this kind of behavior (termed "metamorphism" in a 2008 commentary by Alexey Murzin) suggests a means by which proteins could evolve from one structure to another without losing foldedness or function. Recently, a group from the Weizmann Institute published results in PNAS that speak to this possibility.Although we are most familiar with the circadian rhythm from its effects on our physiological state, the roots of the phenomenon lie in the molecular biology of individual cells. The circadian rhythm is the result of a transcriptional control system that regulates the levels of many different proteins in the cell with the passing of time. Not all of the proteins subject to this control have yet been catalogued, and as a result some surprising effects are still being discovered. A recent article in Proceedings of the National Academy of Sciences from the Sancar lab at UNC suggests that circadian control of a DNA repair factor may be a way to enhance the effectiveness of a chemotherapeutic agent. The article is open access, so I encourage you to open it up and read along.
A protein has several different levels of structure. The primary structure is the arrangements of atoms and bonds, and it is formed in the ribosome by the assembly of amino acids as directed by an RNA template. The secondary structure is the local topology, the helices and strands, and this forms mostly because of the release of energy through the formation of hydrogen bonds. The tertiary structure is the actual fold of the protein, the way helices, strands, and loops are arranged in space. The fold forms primarily because of the favorable entropy of burying the protein's hydrophobic groups where water cannot access them, analogous to the formation of an oil droplet in water. This suggests that, in addition to the well-known phenomenon of proteins denaturing, or losing their higher-order structure, under conditions of high heat, proteins might also denature when they get too cold.The proposition that general fold architecture is preserved within a family of evolutionarily-related proteins is not controversial. The amino acid sequence of a protein determines its structure, and countless studies have substantiated the idea that proteins with similar sequences will adopt similar folded conformations. Because structure and dynamics are intrinsically linked, one could reasonably assume that many features of a protein's dynamics get conserved along with the fold. A growing number of experiments show that this is indeed the case, including a recent paper in Structure (1).Alert your labmates
if your prep will require all
the lab's baffled flasks.
Refill or reorder
reagents before you empty
the goddamn bottle.
Touching toxins, gloves
go on. Touching telephones,
take those nasty things off.
Read the rest...
Final Status: Complete.
Put this on your box: It's Star Fox without anything that you liked about Star Fox!
The ultimate Camp statement: it's good because it's awful. ...Of course, one can't always say that.
—Susan Sontag, "Notes on 'Camp'"
This game is so bad, it's not just become good. It's pretty close to perfect.
—Jim Sterling, review of Deadly Premonition
