On the effect of cosolutes and crowders in the stability and kinetic properties of proteins

Abstract

[EN]It is known since long time that life is present in every environment on Earth, however, this fact results surprising, since some of such environments are characterized by conditions that seem to be incompatible with the survival. To avoid death due to extreme conditions, life has been obligated to adapt, although the mechanism to achieve this depends on the specific condition and, in general, it is still not completely understood. Despite this, something results evident when studying how the organisms that thrive in extreme environments have adapted; that the extreme conditions force the adaptation of the organism at a molecular level, forcing to optimize the stability of biomolecules, and in particular that of the proteins. Proteins perform a great number of functions inside the cells, from structural to production of energy. Because the proteins, for the most part, require a three-dimensional structure to be active, and because the property that guarantees that they preserve such structure is its stability, the loss of the later poses a severe problem for the cells. Aiming to adapt the stability of the proteins to their biological role, Nature has developed multiple strategies that involve a complex machinery capable of modulating the effective concentration of the proteins in the cell. Such machinery emerges from the interconnexion between a wide system of reactions and processes tightly regulated and is sustained by a structural organization level based on weak intermolecular interactions. Having said all this, great part of the homeostasis of a protein is ultimately a function of its amino acid composition. In this context, the surface is the responsible of interacting with the external medium, including the rest of biomolecules. Attending to this fundamental fact, it seems rationale to consider the protein surface as responsible of the sensitivity to the environment and, in consequence, to attribute it a role of relevance in the adaptation mechanisms. Out of all the adaptation mechanisms to extreme environments, that of the adaptation to hypersaline environments (haloadaptation) constitutes a clear example of how protein surfaces have been remodeled exclusively to preserve the stability in presence of high amounts of salt (KCl and other inorganic salts) and/or other cosolutes. This adaptive example can serve as guide for building of a general model of the contribution of the environment to the stability of the proteins (quinary structure). Apart from this, as part of this work, it has also been considered relevant to study what influence poses the own environment on some processes of protein stability loss, particularly the oligomerization reactions through domain swapping. These processes are of special interest due to their implication in some principal cell functions and because of their role in the appearance of several diseases. In summary, this work is oriented to try to extend the haloadaptation mechanism and to extract the keys required to build a model to evaluate the contribution of the environment to the stability of the proteins (quinary structure), as well as to study the influence of the own environment on the oligomerization processes that occur via domain swapping.