功能内稳态
内稳态是生理学的古老概念。
本人将内环境稳定发展成为功能稳定（function-specific homeostasis, FSH）。
在现代生物学的范畴，功能的载体就是蛋白质。功能的稳定意味着相关蛋白质的某种稳定。
附录一是今天的Science对Bemporad等人（2008）工作的评论，可以用来注解功能稳定性。
附录一 Close Enough
The classical view that protein function is associated with a well-defined three dimensional fold has been eroded, slightly, by the discoveries that intrinsically disordered proteins do exist and that disorder might play an important role in protein interactions. Catalysis would seem more structurally demanding. Although it is increasingly recognized that dynamics contributes to enzyme activity, most would have assumed that this occurs in the context of a folded protein; nevertheless, catalytic activity has been observed in an engineered enzyme with molten globule properties, where activity is apparently coupled to substrate-induced folding. Bemporad et al. show that the partially folded Sulfolobus solfataricus acylphosphatase is active and that this does not derive from a global substrate-induced folding. Molecular dynamics simulations revealed that an ensemble of partly folded molecules is characterized by substantial structural flexibility of the catalytic region; the remainder of the protein forms a scaffold that restricts the conformational space of the flexible region so that in a large fraction of the ensemble, residues important for catalysis remain close together. The authors suggest that scaffold regions in proteins might allow functional regions to mutate without compromising overall stability, thus facilitating the evolution of new activities. It remains to be seen if this is a rare case or whether catalysis in the absence of well-defined folded structure is a more common but underappreciated enzyme property
Bemporad F, Gsponer J, Hopearuoho HI, Plakoutsi G, Stati G, Stefani M, Taddei N, Vendruscolo M, Chiti F. 2008. Biological function in a non-native partially folded state of a protein. EMBO J. 2008 May 21;27(10):1525-35. As structural flexibility is known to be required for enzyme catalysis and pattern recognition and a significant fraction of eukaryotic proteins appear to be unfolded or contain unstructured regions, biological activity of conformational states distinct from fully folded structures could be more common than previously thought. By applying a procedure that allows the recovery of enzymatic activity to be monitored in real time, we show that a non-native state populated transiently during folding of the acylphosphatase from Sulfolobus solfataricus is enzymatically active. The structural characterization of this partially folded state reveals that enzymatic activity is possible even if the catalytic site is structurally heterogeneous, whereas the remainder of the structure acts as a scaffold. These results extend the spectrum of biological functions carried out in the absence of a folded state to include enzyme catalysis.
[ 本帖最后由 刘承宜 于 2008-5-30 06:45 AM 编辑 ]
