Antiaggregation Activity of Chaperones and Its Quantification

The spacial structure of proteins is rather labile and depends on external conditions. Stress conditions can cause formation of unfolded protein forms that exhibit enhanced tendency to aggregation. During biosynthesis of proteins in cells, folding of the newly synthesized polypeptide chains can be accompanied by formation of non-native protein forms with a tendency to aggregate The family of small heat shock proteins (sHsp) has a special place among the heat shock proteins; the main function of sHsp is suppression of aggregation of nonnative protein forms. Representatives of this family are found in almost all living organisms. The low molecular mass of monomers (from 12 to 43 kDa) and tendency to formation of large oligomers with molecular masses up to 1000 kDa are typical of this protein family sHsp-protein substrate complexes are characterized by a high degree of polydispersity REVIEW 1554 Abbreviations: GAPDH, glycerlaldehyde-3-phosphate dehydrogenase; HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; Phb, glycogen phosphorylase b; sHsp, small heat shock protein

Phase appearance or disappearance in two-phase flows

This paper is devoted to the treatment of specific numerical problems which appear when phase appearance or disappearance occurs in models of two-phase flows. Such models have crucial importance in many industrial areas such as nuclear power plant safety studies. In this paper, two outstanding problems are identified: first, the loss of hyperbolicity of the system when a phase appears or disappears and second, the lack of positivity of standard shock capturing schemes such as the Roe scheme. After an asymptotic study of the model, this paper proposes accurate and robust numerical methods adapted to the simulation of phase appearance or disappearance. Polynomial solvers are developed to avoid the use of eigenvectors which are needed in usual shock capturing schemes, and a method based on an adaptive numerical diffusion is designed to treat the positivity problems. An alternate method, based on the use of the hyperbolic tangent function instead of a polynomial, is also considered. Numerical results are presented which demonstrate the efficiency of the proposed solutions

Hysteretic Behavior of Proprotein Convertase 1/3 (PC1/3)

The proprotein convertases (PCs) are calcium-dependent proteases responsible for processing precursor proteins into their active forms in eukariotes. The PC1/3 is a pivotal enzyme of this family that participates in the proteolytic maturation of prohormones and neuropeptides inside the regulated secretory pathway. In this paper we demonstrate that mouse proprotein convertase 1/3 (mPC1/3) has a lag phase of activation by substrates that can be interpreted as a hysteretic behavior of the enzyme for their hydrolysis. This is an unprecedented observation in peptidases, but is frequent in regulatory enzymes with physiological relevance. The lag phase of mPC1/3 is dependent on substrate, calcium concentration and pH. This hysteretic behavior may have implications in the physiological processes in which PC1/3 participates and could be considered an additional control step in the peptide hormone maturation processes as for instance in the transformation of proinsulin to insulin

Global Self-Organization of the Cellular Metabolic Structure

Background: Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using "metabolic networks models'' are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used "dissipative metabolic networks'' (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. Methodology/Principal Findings: Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. Conclusions/Significance: This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures.Supported by the Spanish Ministry of Science and Education Grants MTM2005-01504, MTM2004-04665, partly with FEDER funds, and by the Basque Government, Grant IT252-07