FEBS Journal

Transient protein complexes, with short lifetimes, are the result of compromise between the specificity and the instability of the binding. For metalloproteins, such features are even more pronounced because they are often engaged in electron transfer processes. Understanding the dynamics of the redox transient metallo-interactome and, in particular, of the interactions involving biomimetic interfaces requires a challenge based on specific proteomic tools.

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The review focuses on the effects of local electric fields on cytochrome c bound to coated electrodes. For such devices that mimic the electrostatic properties of biological membranes surface-sensitive spectroelectrochemicals allow for an in-depth analysis of the molecular processes of the immobilised cytochrome c, contributing to a better understanding of the potential electric–field dependent control of the protein’s function.

Recent NMR studies demonstrated that the encounter state plays an important role in the formation of transient complexes of electron transfer proteins. The fine balance between the encounter state and the productive complex makes it possible to meet the opposing requirements of rapid electron transfer and a high turn-over rate. (Thumbnail reprinted with permission from [20]. Copyright 2008 American Chemical Society).

Metalloproteins play major roles in cell metabolism and signaling pathways, showing a moonlighting behaviour, which depends on the physiological state of the cell. Understanding these multitasking proteins compels us to discover their partners with which to carry out such novel functions. We gather the different proteomic techniques and biointeractomic tools, whose applicability to the study of transient protein–protein interactions make them suitable for metalloprotein interactions.

This introduction to the minireview series focuses on the emerging regulatory roles of hyaluronan in health and disease. The series describes the novel mechanism for biosynthesis of hyaluronan and fresh insights on the roles of its interaction with variants of the cell surface receptor CD44. These aspects provide the basis for the exceptional versatility of hyaluronan in normal and pathological processes, including diabetes and cancer.

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Hyaluronan matrices are ubiquitous in normal and pathological biological processes. The mechanisms involve active hyaluronan synthases at the cell membrane when cell stresses occur in physiological levels of glucose. However, dividing cells in hyperglycemic levels of glucose initiate synthesis of hyaluronan in intracellular compartments, which induces endoplasmic reticulum stress and autophagy, processes that likely contribute greatly to diabetic pathologies.

Changes in the content, molecular mass and turnover rate of hyaluronan are crucial for cell proliferation, migration, and apoptosis, processes that control tissue remodeling during embryonic development, inflammation, injury and cancer. Here, transcriptional regulation of hyaluronan synthase (Has1-3), post-translational control of HAS activity and the supply of the UDP-sugar substrates of HAS are highlighted as regulators of hyaluronan synthesis.

CD44 family of transmembrane glycoprotein is comprised of members that differ in the extracellular domain where 10 variant exons are inserted. Hyaluronan induces signaling when it binds to CD44 variants (CD44v) in cancer/inflammatory disease. CD44v were implicated in tumorigenesis due to its selective binding to growth-factors and their receptor-tyrosine-kinases. Accordingly targeting specific CD44v by appropriate shRNA can be useful for cancer therapy.

Newly synthesized alizarine analogues inhibited both HIV-1 wild-type reverse transcriptase (RT)-associated DNA polymerase and RNase H functions, and retained their inhibitory effect also on the RT-associated RNase H function of K103N and Y181C RTs. Mechanism of action studies, docking experiments and molecular dynamic simulation showed that they are allosteric inhibitors and occupy a binding pocket close to the NNRTI site.

The histone demethylase JARID1A was identified as an estrogen receptor (ER)α cofactor controlling progesterone receptor (PR) expression. Reduction of JARID1A in MCF-7 cells led to enhanced PR expression whereas JARID1A overexpression suppressed activity of a PR promoter reporter construct. Chromatin immunoprecipitation showed that JARID1A bound to the PR gene upstream region. Reducing JARID1A levels led to higher H3K4 trimethylation in this region.

We here report the molecular mechanism underlying the annexin IV expression in ovarian clear cell adenocarcinoma cells. We identified tandem repeats corresponding to the motif for p53 binding in the first intron of annexin A4, and revealed that functional status of p53 is involved in the gene regulation.

Cytochrome P450 2E1 (CYP2E1) is an effective generator of reactive oxygen species. In this study we provided evidence that expression of CYP2E1 was strongly up-regulated in cTnT^R141W transgenic mice with dilated cardiomyopathy (DCM). The overexpression of CYP2E1 caused DCM phenotype, cardiac oxidative stress and myocyte apoptosis, all of which were similar to that in cTnT^R141W transgenic mice.

Mutations in the transmembrane domain of rhodopsin, associated with retinitis pigmentosa, present altered photobleaching patterns. These are characterized by the formation of non-functional metarhodopsin I-like photointermediates that would abnormally accumulate, causing toxic effects on photoreceptor cells and leading to their degeneration. This finding adds on the complexity of molecular mechanisms, other than protein misfolding, associated with retinitis pigmentosa retinal degeneration.

Replacing Cu-ligand His117 by glycine in azurin leads to increased flexibility of the ligand loop and a gap in the Cu coordination shell that is partly filled with water molecules. Flash photolysis experiments show that His117 acts as an electronic conduit for electron transfer; the water molecules in the H117G variant are less efficient in this respect.

The mechanisms whereby chronic liver diseases develop hepatic fibrosis remain incompletely defined. In our study we found that microRNA became dysregulated in dimethylnitrosamine-induced hepatic fibrosis in rats. Gene ontology analysis further showed that many of these dysregulated miRNAs were involved in lipid/fatty acid metabolism. The upregulated miR-34 family may be involved in the hepatic fibrosis process by targeting ACSL1.

The post-transcriptional regulatory element (PRE) element of HBV harbors a 105-nucleotide element that functions as an intronic splicing silencer (ISS), largely through forming a double-hairpin structure rather than primary sequences. The silencing function decreases with the distance from affected splice sites. These findings highlight novel roles of RNA structure in repressing the usage of alternative and cryptic splice sites.

This work introduces an explicit kinetic model for the initial burst in the activity of cellulolytic enzymes. Application of the model to calorimetric data for the exocellulase Cel7A suggests that the burst phase occurs as a result of rapid adsorption and processive movement on the cellulose strand but slow dissociation of enzymes stalled at obstacles on the strand.

Importin α functions as a nuclear transport receptor. We generated mice deficient for importin α5, which is one of six importin α isoforms in mice, and demonstrated that importin α5 plays essential roles in the mammalian female reproductive organs. Our studies on importin α5 knockout mice identified a novel risk factor that causes female infertility and/or the difficulty in parturition.

Three novel avian cathelicidin orthologues were cloned encoding three antimicrobial peptides of 26, 32, 29 amino acid residues length. Synthetic Cc-CATH2 and 3 displayed broad and potent antimicrobial activity. Cc-CATH2 and 3 showed much reduced cytotoxicity, and a negligible hemolytic activity, lysing only 3.6% of erythrocytes at doses up to 100 μg·mL⁻¹. Recombinant Cc-CATH2 showed potent bactericidal activity as expected.

Ascorbate oxidase (AAO) is a large, multidomain, dimeric protein whose folding/unfolding pathway is characterized by a complex, multistep process. Fluorescence correlation spectroscopy was used to demonstrate the formation of partially folded monomers by pH-induced full dissociation into subunits. The structural features of monomeric AAO have been characterized by fluorescence and circular dichroism spectroscopy.