FEBS Journal

Here a brief introduction to the series is given, which highlights concepts, recent findings and current challenges in understanding chaperone function and quality control of proteins.

The long-term health of all metazoan cells is linked to protein quality control. Studying the regulation of cellular protein folding homeostasis (proteostasis) in the context of the whole organism has unraveled multiple layers of cell-nonautonomous regulation. Here, we discuss emerging concepts in cell-nonautonomous regulation of protein quality control networks that may present novel, yet general targets for misfolding disease intervention.

In their natural environment cells are regularly exposed to various stress conditions, which may lead to protein misfolding and the formation of harmful protein aggregates. To deal with the misfolded proteins, cells have evolved various counter measures; including refolding by molecular chaperones and targeting misfolded proteins to the ubiquitin-proteasome system. We review the interplay between the chaperone and degradation systems.

Only a small subset of E. coli proteins require the GroE chaperone system for folding in vivo under normal conditions. It remains unclear, however, why some proteins need GroE and others do not. Here, we review experimental and computational studies that compared various properties of GroE substrates with those of non-substrates and show that predicting GroE-dependency remains a challenge.

Myosins are molecular motors that power essential motility functions in the cell, and structural biology is an important tool to decipher how these motors work. Functional and structural studies have provided detailed understanding of the motor rearrangements that allow conversion of chemical energy into force production. In particular, studies on a reverse motor have been very insightful since they solved a number of puzzling and controversial enigmas about how this motor produces force, extends its lever arm and dimerizes.

Myeloid leukemia factor 1 (MLF1) is a protein implicated in the development of acute myeloid leukaemia. We report the crystal structure of [MLF1(29-42)pSer34] in complex with 14-3-3ε and propose a chemical biology approach employing small molecules that can modulate the MLF1/14-3-3 interaction. As a first step, we present a molecule identified by fragment-based ligand discovery that is binding to the interface of 14-3-3 and MLF1.

Several splice variants are reported for PKA Cβ subunit gene namely Cβ1, Cβ2, Cβ3, Cβ3b, Cβ3ab, Cβ3abc, Cβ4, Cβ4b, Cβ4ab and Cβ4abc. In this study, we have identified three novel alternatively spliced transcript variants of mouse Cβ gene designated Cβ5, Cβ6 and Cβ7 by using bioinformatics tools and molecular biology techniques. These transcript variants differ in their first coding exon.

GalNAc–analogs with modified N–acyl groups are incorporated into cellular O-glycans although to different levels. The GalNAc–analogs linked to Ser or Thr (visualized by Vicia villosa lectin in the Golgi, green) are extended by the β3-galactosyltransferase C1GalT in vitro and in vivo (neuraminidase and peanut lectin at the cell surface, red).The unnatural O-glycans are further extended by sialylation.

Mice with cardiac specific ablation of the insulin sensitive glucose transporter 4 gene (G4H^−/−) have cardiac hypertrophy and a lower ratio of reduced to oxidized glutathione. Cardiac hypertrophy was attenuated by tempol treatment (cell permeable antioxidant), but not MnTBAP (mitochondrial targeted antioxidant). These results indicate that mitochondrial oxidative stress may not contribute to the hypertrophic phenotype of G4H^−/− mice.

d-Serine dehydratase from Saccharomyces cerevisiae is a pyridoxal 5′-phosphate- and Zn²⁺-dependent enzyme catalyzing d-serine dehydration. The Zn²⁺ is indispensable for the elimination of hydroxyl group of substrate. ¹H NMR determined the rates of α-hydrogen abstraction and hydroxyl group elimination of d-serine in ²H₂O and revealed that the α-hydrogen abstraction and hydroxyl group elimination occur in a concerted fashion.

TM4SF5 induces epithelial-mesenchymal transition for an enhanced migration and a contact inhibition loss. Here, TM4SF5 was induced by TGFβ1 and EGF signaling pathways in hepatocytes in vitro and CCl₄-adminstrated mice in vivo, together with induction of liver fibrotic features along the fibrotic septa, which were blocked by treatment with anti-TM4SF5 reagent, TSAHC. These suggest that TM4SF5 expression has a function in liver fibrosis.

Phylogenetic analysis of the conserved domains of secreted phospholipases A₂ (sPLA₂s) revealed that two main clades, the cd- and the pfam-collection have evolved via gene duplication and deletion events. The observations indicate that sPLA₂s in eukaryotes shared common origins with two types of bacterial sPLA₂s and their persistence during evolution may be related to their role in phospholipid metabolism which is fundamental for survival.

G_αs-transfected s49 cyc- cells showed more sensitization of adenylyl cyclase following chronic morphine compared to non-transfected cells. Ser/Thr mutation to Ala at α3/β5 loop of G_αs, enhanced morphine-induced adenylyl cyclase sensitization. α3/β5 or α4/β6 mutants did not change morphine inhibition or isoproterenol simulation of adenylyl cyclase. Furthermore they did not affect the pattern or extent of ERK1/2 phosphorylation by isoproterenol/morphine.