Current Protein and Peptide Science - Volume 16, Issue 2, 2015

Polysaccharide and proteins are the major constituent building blocks of biological systems and often occur as highly organized macromolecular architectures (e.g. the capsid of viruses). Both can occur in the same or in different biological physiological environment interacting in specific or non-specific ways. When isolated and purified, these macromolecules can harness self-assembled (SA) soft nanomaterials by non-covalent electrostatic complexation. Although polysaccharide-protein electrostatic SA systems of this type have been studied for more than two decades, the possibility to design materials with enhanced biological function and improved technological advantages over those based on synthetic or inorganic components, has only started to be recognized and is yet to be fully realized. In this review we address two main type of SA polysaccharideprotein systems, namely, those based on chitosan-protein and those based on polyanionic polysaccharide (pectin, hyaluronic acid or alginate) - protein ones. The physical properties of chitosan- and polyanion-based SA nanocomplexes with oppositely charged proteins depend on the composition and conditions as reviewed here with reference to some specific systems.

Reduction in fossil fuel consumption by using alternate sources of energy is a major challenge facing mankind in the coming decades. Bioethanol production using lignocellulosic biomass is the most viable option for addressing this challenge. Industrial bioconversion of lignocellulosic biomass, though possible now, is not economically viable due to presence of barriers that escalate the cost of production. As cellulose and hemicellulose are the major constituents of terrestrial biomass, which is available in massive quantities, hydrolysis of cellulose and hemicellulose by the microorganisms are the most prominent biochemical processes happening in the earth. Microorganisms possess different categories of proteins associated with different stages of bioethanol production and a number of them are already found and characterized. Many more of these proteins need to be identified which suit the specificities needed for the bioethanol production process. Discovery of proteins with novel specificities and application of genetic engineering technologies to harvest the synergies existing between them with the aim to develop consolidated bioprocess is the major direction of research in the future. In this review, we discuss the different categories of proteins used for bioethanol production in the context of breaking the barriers existing for the economically feasible lignocellulosic bioethanol production.

Pathogenic aggregation is closely associated with various protein misfolding diseases such as type 2 diabetes mellitus and Alzheimer’;s disease. Amyloidogenic proteins that have a propensity to assemble into amyloid oligomers and fibrils form the aggregates. The tumor suppressor p53, a transcription factor that regulates the cell cycle and apoptosis, is also amyloidogenic. In tumor models, both wild type and mutant p53 proteins show aggregation kinetics and morphology similar to those of classical amyloidogenic proteins, such as β-amyloid peptide and α- synuclein. Wild type p53 loses its anticancer activity when it aggregates, while p53 mutants with enhanced amyloidogenicity show accelerated aggregation. So far, amyloidogenic p53 mutations have been implicated in more than ten different types of cancer, suggesting a connection between p53 aggregation and cancer. Therefore, inhibition of both inherent and mutation induced p53 aggregation may stabilize p53 in a functional conformation and provide a novel approach to cancer prevention and treatment. Here, we summarize recent findings on carcinogenic aggregation of wild type p53 and its clinical mutants, structure-dependent amyloidogenesis of p53, and several promising strategies based on inhibition of p53 aggregation are also discussed.

Proline-rich peptides (PRPs) include a large and heterogeneous group of small-medium sized peptides characterized by the presence of proline residues often constituting peculiar sequences. This feature confers them a typical structure that determines the various biological functions endowed by these molecules. In particular the left-handed-polyproline-II helix is essential for the expression of the antimicrobial, immunomodulatory, antioxidant properties and to finely modulate protein-protein interactions, thus playing crucial roles in many cell signal transduction pathways. These peptides are widely diffuse in the animal kingdom and in humans, where they are present in many tissues and biological fluids. This review highlights the most relevant biological properties of these peptides, focusing on the potential therapeutic role that the PRPs may play as a promising source of new peptidebased novel drugs.

The N-end rule pathway is a conserved targeted proteolytic process observed in organisms ranging from eubacteria to mammals. The N-end rule relates the metabolic stability of a protein to its N-terminal amino acid residue. The identity of the N-terminal amino acid residue is a primary degradation signal, often referred to as an N-degron, which is recognized by the components of the N-end rule when it is a destabilizing N-terminus. N-degrons may be exposed by non-processive proteolytic cleavages or by post-translational modifications. One modification is the post-translational addition of amino acids to the N-termini of proteins, a reaction catalyzed by aminoacyl-tRNA protein transferases. The aminoacyl-tRNA protein transferase in eubacteria like Escherichia coli is L/F transferase. Recent investigations have reported unexpected observations regarding the L/F transferase catalytic mechanism and its mechanisms of substrate recognition. Additionally, recent proteome-wide identification of putative in vivo substrates facilitates hypothesis into the yet elusive biological functions of the prokaryotic N-end rule pathway. Here we summarize the recent findings on the molecular mechanisms of catalysis and substrate recognition by the E. coli L/F transferase in the prokaryotic N-end rule pathway.