One purpose of protein engineering is obviously the molecular design of proteins being stable against heat. Thermostability of globular proteins is generally discussed in two different terms; one is the thermodynamic stability and the other is the stability as evaluated from kinetic behaviors of inactivation process. The strict characterization of thermodynamic stability can be made only when the protein denatures reversibly. In contrast the irreversible denaturation of proteins is quantitatively studied in most cases by measuring the rate of thermally induced activity loss at set temperatures. Although these two terms involve the quite different nature, they are sometimes mixed up with each other so that all the discussions are in vain. In this article the protein stability as derived from these two different aspects is compared and the suggestion is made that for further advancement in protein engineering it is essentially important to clarify the reactivity of unfolded proteins yielding aggregation.
Anfinsen's classical work demonstrated that refolding of many proteins from their denatured states is spontaneous process. In recent years, however, a number of proteins which are involved in folding of other proteins have been discovered. This family of proteins is termed molecular chaperones. In this article we discuss the structure and function of chaperonin, one of the well-studied molecular chaperones. Furthermore, an extending concept of molecular chaperones, "From the cradle to the grave" is introduced.
Hydration of a protein molecule significantly influences its thermodynamic stability. Cold denaturation and pressure denaturation are considered to be induced by this effect. These phenomena are closely related to the hydration effect on several thermodynamic functions; enthalpy, entropy, heat capacity, volume and compressibility. The macroscopic and microscopic views of these thermodynamic functions are also discussed.
As a prediction from the scaled particle theory, the solvent exclusion effect due to introduction of nonpolar solutes into water is shown to be an important factor of the hydrophobic effect. Based on this view, structural and energetic aspects of hydrating water are discussed.
At present, there are two contradictory views about the molten globule state as a kinetic intermediate of protein folding. One view demonstrates that it is formed immediately after refolding starts, so that both the formation of secondary structure and the compaction of a protein molecule are very rapid, occurring within several milliseconds. The opposing view demonstrates that the molten globule is formed more slowly with a half time up to several hundred milliseconds, and this process occurs only after formation of secondary structure. These two views are discussed, and the experimental as well as theoretical studies that support each of the two views are described.
Structural information about an unfolded state is important for the better understanding of both protein folding and protein itself. Compactness and chain statistics which are essential to characterize an unfolded state are derived by X-ray solution scattering method. In this article, the author describes the examples of studies on a protein unfolded state, such as urea denaturation of Staphylococcal nuclease, acid-denatured and molten globule states of cytochrome c, and a Staphylococcal nuclease fragment which is an unfolded state under a physiological condition. These examples suggest diversity of protein unfolded state.
Double helix formation of egg-yolk phosphatidylcholine myelin figures has been studied by use of an optical microscopy. The double helices were looser than a geometrically possible one and the pitchs were related proportionaly to the outer radii of helical myelin figures. The regularity in the winding was explained in terms of the intermembrane binding energy and the bending elastic energy of helical myelin figures.
Recently the mesoderm inducing factors related with growth factors have reported exponentially in the world. Especially FGF and activin seem to be the natural inducing factors. We report here the recent works of these factors concerning with the gene expression and cell differentiation. Activin and FGF can express the several kinds of homeotic genes including Mix.1, goosecold. Xhox3, Xlim-1 etc. in the presumptive ectoderm. These mesoderm inducing factors control the gene expression and cell differentiation subsequently as like as normal development in Xenopus. The possible molecular mechanisms of signal transduction of these factors are also reported in this paper.