How hydrophobicity shapes the architecture of protein assemblies.

The interactions that give rise to protein self-assembly are basically electrical and hydrophobic in origin. The electrical interactions are approached in this study as the interaction between electrostatic dipoles originated by the asymmetric distribution of their charged amino acids. However, hydrophobicity is not easily derivable from basic physicochemical principles.

Pathogen Moonlighting Proteins: From Ancestral Key Metabolic Enzymes to Virulence Factors.

Moonlighting and multitasking proteins refer to proteins with two or more functions performed by a single polypeptide chain. An amazing example of the Gain of Function (GoF) phenomenon of these proteins is that 25% of the moonlighting functions of our Multitasking Proteins Database (MultitaskProtDB-II) are related to pathogen virulence activity. Moreover, they usually have a canonical function belonging to highly conserved ancestral key functions, and their moonlighting functions are often involved in inducing extracellular matrix (ECM) protein remodeling.

The importance of hydrophobic interactions in the structure of transcription systems.

Hydrophobic forces play a crucial role in both the stability of B DNA and its interactions with proteins. In the present study, we postulate that the hydrophobic effect is an essential component in establishing specificity in the interaction transcription factor proteins with their consensus DNA sequence partners. The PDB coordinates of more than 50 transcription systems have been used to analyze the hydrophobic attraction of proteins towards their DNA consensus.

A protein self-assembly model guided by electrostatic and hydrophobic dipole moments.

Protein self-assembling is studied under the light of the Biological Membrane model. To this purpose we define a simplified formulation of hydrophobic interaction energy in analogy with electrostatic energy stored in an electric dipole. Self-assembly is considered to be the result of the balanced influence of electrostatic and hydrophobic interactions, limited by steric hindrance as a consequence of the relative proximity of their components.

Multifunctional Proteins: Involvement in Human Diseases and Targets of Current Drugs.

Multifunctionality or multitasking is the capability of some proteins to execute two or more biochemical functions. The objective of this work is to explore the relationship between multifunctional proteins, human diseases and drug targeting. The analysis of the proportion of multitasking proteins from the MultitaskProtDB-II database shows that 78% of the proteins analyzed are involved in human diseases.

A hypothesis explaining why so many pathogen virulence proteins are moonlighting proteins.

Moonlighting or multitasking proteins refer to those proteins with two or more functions performed by a single polypeptide chain. Proteins that belong to key ancestral functions and metabolic pathways such as primary metabolism typically exhibit moonlighting phenomenon. We have collected 698 moonlighting proteins in MultitaskProtDB-II database.

MultitaskProtDB-II: an update of a database of multitasking/moonlighting proteins.

Multitasking, or moonlighting, is the capability of some proteins to execute two or more biological functions. MultitaskProtDB-II is a database of multifunctional proteins that has been updated. In the previous version, the information contained was: NCBI and UniProt accession numbers, canonical and additional biological functions, organism, monomeric/oligomeric states, PDB codes and bibliographic references.

Vector description of electric and hydrophobic interactions in protein homodimers.

This article describes the formation of homodimers from their constituting monomers, based on the rules set by a simple model of electric and hydrophobic interactions. These interactions are described in terms of the electric dipole moment (D) and hydrophobic moment vectors (H) of proteins. The distribution of angles formed by the two dipole moments of monomers constituting dimers were analysed, as well as the distribution of angles formed by the two hydrophobic moments.

A model of protein association based on their hydrophobic and electric interactions.

The propensity of many proteins to oligomerize and associate to form complex structures from their constituent monomers, is analyzed in terms of their hydrophobic (H), and electric pseudo-dipole (D) moment vectors. In both cases these vectors are defined as the product of the distance between their positive and negative centroids, times the total hydrophobicity or total positive charge of the protein. Changes in the magnitudes and directions of H and D are studied as monomers associate to form larger complexes.

MultitaskProtDB: a database of multitasking proteins.

We have compiled MultitaskProtDB, available online at http://wallace.uab.es/multitask, to provide a repository where the many multitasking proteins found in the literature can be stored.

How budding yeast sense and transduce the oxidative stress signal and the impact in cell growth and morphogenesis.

The eukaryotic microorganism Saccharomyces cerevisiae is a current model system in which to study the signal transduction pathways involved in the oxidative stress response. In this review we present the current evidence demonstrating that in S. cerevisiae several MAPK and signalling routes participate in this response (PKC1-MAPK, TOR, RAS-PKA-cAMP).

The regulatory action of alpha-actinin on actin filaments is enhanced by cofilin.

We have used fluorescence recovery after photobleaching to study the effect of muscle alpha-actinin on the structure of actin filaments in dilute solutions. Unexpectedly we found that alpha-actinin partitioned filaments into two types: those with a high mobility and those with low mobility. We have determined that the high mobility (smaller sized) population is too large to be simple monomeric actin:alpha-actinin complexes.

Two proteins from Saccharomyces cerevisiae: Pfy1 and Pkc1, play a dual role in activating actin polymerization and in increasing cell viability in the adaptive response to oxidative stress.

In this work, we show that the proteins Pkc1 and Pfy1 play a role in the repolarization of the actin cytoskeleton and in cell survival in response to oxidative stress. We have also developed an assay to determine the actin polymerization capacity of total protein extracts using fluorescence recovery after photobleaching techniques and actin purified from rabbit muscle. This assay allowed us to demonstrate that Pfy1 promotes actin polymerization under conditions of oxidative stress, while Pkc1 induces actin polymerization and cell survival under all the conditions tested.

Hydrophobicity density profiles to predict thermal stability enhancement in proteins.

A hydrophobicity density is defined for a protein through its hydrophobicity tensor (similar to the inertia tensor), by using the Eisenberg hydrophobicity scale of the hydrophobic amino acids of a protein. This allows calculation of the radii of the corresponding hydrophobic ellipsoid of a protein and thus subsequently of its hydrophobic density. A hydrophobicity density profile is then obtained by simulating point mutations of each amino acid of a protein either to a high hydrophobicity value or to zero hydrophobicity.

Study of the influence of temperature on the dynamics of the catalytic cleft in 1,3-1,4-beta-glucanase by molecular dynamics simulations.

The dependence of some molecular motions in the enzyme 1,3-1,4-beta-glucanase from Bacillus licheniformis on temperature changes and the role of the calcium ion in them were explored. For this purpose, two molecular dynamics simulated trajectories along 4 ns at low (300 K) and high (325 K) temperatures were generated by the GROMOS96 package. Several structural and thermodynamic parameters were calculated, including entropy values, solvation energies, and essential dynamics (ED).

A simple electrostatic criterion for predicting the thermal stability of proteins.

The enhancement of protein thermostability is an important issue for both basic science and biotechnology purposes. We have developed a thermostability criterion for a protein in terms of a quasi-electric dipole moment (contributed by its charged residues) defined for an electric charge distribution whose total charge is not zero. It was found that minimization of the modulus of this dipole moment increased its thermal stability, as demonstrated by surveying these values in pairs of mesostable-thermostable homologous proteins and in mutations described in the literature.