Published by De Gruyter

Volume 393 Issue 11

Issue of Biological Chemistry

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Contents
Journal Overview

Masthead

Publicly Available October 11, 2012

Guest Editorial

October 11, 2012

Highlight: Membrane transport and beyond

Dirk Schneider, Lutz Schmitt

Page range: 1201-1202

Abstract

No abstract available.

Highlight: Membrane Transport and Beyond

Publicly Available October 11, 2012

Structure and function of bacterial dynamin-like proteins

Marc Bramkamp

Page range: 1203-1214

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Abstract

Membrane dynamics are essential for numerous cellular processes in eukaryotic and prokaryotic cells. In eukaryotic cells, membrane fusion and fission are often catalyzed by large GTPases of the dynamin protein family. These proteins couple GTP hydrolysis to membrane deformation, which eventually leads to fusion or fission of the lipid bilayer. Mutations in eukaryotic dynamin-like proteins (DLPs) are associated with various diseases underscoring the importance to fully understand the biochemistry of these proteins. In recent years, a wealth of structural and biochemical data have been published that allow a detailed analysis of how dynamins or DLPs modulate biological membranes. However, less is known about the function of bacterial DLPs, although structural data exist. This review summarizes current knowledge about bacterial dynamins and discusses structural and functional properties in comparison to their eukaryotic counterparts.

October 11, 2012

Oligomerization of polytopic α-helical membrane proteins: causes and consequences

Florian Cymer, Dirk Schneider

Page range: 1215-1230

Abstract

Several polytopic α-helical membrane-integrated proteins appear to be organized in higher-ordered oligomeric complexes. While many aspects are still enigmatic, in recent years, the physiological impact of membrane protein oligomerization has been analyzed to some extent. In the present article, oligomerization of structurally well-defined membrane proteins is discussed. The available experimental information indicates the causes and physiological consequences of membrane protein oligomerization, including stabilization, cooperative functions, and control of specific activities. Based on the currently available observations, we aim to derive some general principles and discuss open questions.

October 11, 2012

Functional relevance of transmembrane domains in membrane fusion

Jörg Nikolaus, Andreas Herrmann

Page range: 1231-1245

Abstract

Membrane fusion is ubiquitous in life. Fusion of biological membranes is mediated by specialized fusion proteins anchored to the bilayers destined to fuse. Here we describe these proteins as being instrumental in viral, intracellular and developmental fusion. Next, we review experimental and theoretical evidence that points to fusion in the different systems as following a common ‘fusion through hemifusion’ pathway. We also focus on the structure and dynamics of the transmembrane segment that anchors the fusion proteins to the bilayer, and its role in driving fusion. In particular, we highlight the influence of this single segment on the surrounding membrane lipids and on the overall shape of the membrane along the way to fusion.

Publicly Available October 11, 2012

Mitofilin complexes: conserved organizers of mitochondrial membrane architecture

Ralf M. Zerbes, Ida J. van der Klei, Marten Veenhuis, Nikolaus Pfanner, Martin van der Laan, Maria Bohnert

Page range: 1247-1261

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Abstract

Mitofilin proteins are crucial organizers of mitochondrial architecture. They are located in the inner mitochondrial membrane and interact with several protein complexes of the outer membrane, thereby generating contact sites between the two membrane systems of mitochondria. Within the inner membrane, mitofilins are part of hetero-oligomeric protein complexes that have been termed the mitochondrial inner membrane organizing system (MINOS). MINOS integrity is required for the maintenance of the characteristic morphology of the inner mitochondrial membrane, with an inner boundary region closely apposed to the outer membrane and cristae membranes, which form large tubular invaginations that protrude into the mitochondrial matrix and harbor the enzyme complexes of the oxidative phosphorylation machinery. MINOS deficiency comes along with a loss of crista junction structures and the detachment of cristae from the inner boundary membrane. MINOS has been conserved in evolution from unicellular eukaryotes to humans, where alterations of MINOS subunits are associated with multiple pathological conditions.

October 11, 2012

The gateway to chloroplast: re-defining the function of chloroplast receptor proteins

Wai-Ling Chang, Jürgen Soll, Bettina Bölter

Page range: 1263-1277

Abstract

Chloroplast biogenesis often requires a tight orchestration between gene expression (both plastidial and nuclear) and translocation of ∼3000 nuclear-encoded proteins into the organelle. Protein translocation is achieved via two multimeric import machineries at the outer (TOC) and inner (TIC) envelope of chloroplast, respectively. Three components constitute the core element of the TOC complex: a β-barrel protein translocation channel Toc75 and two receptor constituents, Toc159 and Toc34. A diverse set of distinct TOC complexes have recently been characterized and these diversified TOC complexes have evolved to coordinate the translocation of differentially expressed proteins. This review aims to describe the recent discoveries relating to the typical characteristics of these distinct TOC complexes, particularly the receptor constituents, which are the main contributors for TOC complex diversification.

October 11, 2012

The YidC/Oxa1/Alb3 protein family: common principles and distinct features

Manfred J. Saller, Zht Cheng Wu, Jeanine de Keyzer, Arnold J.M. Driessen

Page range: 1279-1290

Abstract

The members of the YidC/Oxa1/Alb3 protein family are evolutionary conserved in all three domains of life. They facilitate the insertion of membrane proteins into bacterial, mitochondrial, and thylakoid membranes and have been implicated in membrane protein folding and complex formation. The major classes of substrates are small hydrophobic subunits of large energy-transducing complexes involved in respiration and light capturing. All YidC-like proteins share a conserved membrane region, whereas the N- and C-terminal regions are diverse and fulfill accessory functions in protein targeting.

October 11, 2012

The sensor kinase DcuS of Escherichia coli: two stimulus input sites and a merged signal pathway in the DctA/DcuS sensor unit

Julian Witan, Christian Monzel, Patrick D. Scheu, Gottfried Unden

Page range: 1291-1297

Abstract

The membrane-integral sensor kinase DcuS of Escherichia coli consists of a periplasmically located sensory PAS P domain, transmembrane helices TM1 and TM2, a cytoplasmic PAS C domain and the kinase domain. Stimulus (C 4 -dicarboxylate) binding at PAS P is required to stimulate phosphorylation of the kinase domain, resulting in phosphoryl transfer to the response regulator DcuR. PAS C functions as a signaling device or a relay in signal transfer from TM2 to the kinase. Phosphorylated DcuR induces the expression of the target genes. Sensing by DcuS requires the presence of the C 4 -dicarboxylate transporter DctA during aerobic growth. DctA forms a sensor unit with DcuS, and a short C-terminal sequence of DctA forming the putative helix 8b is required for interaction with DcuS. Helix 8b contains a LDXXXLXXXL motif that is essential for function and interaction. DcuS requires the PAS C domain for signal perception from DctA. Thus, DcuS and DctA form a DctA/DcuS sensory unit, and DcuS perceives stimuli from two different sites (PAS P and DctA). The signal transfer pathways are supposed to merge at PAS C . The fumarate/succinate antiporter DcuB takes over the role as a co-sensor of DcuS under anaerobic growth conditions.

Reviews

Publicly Available October 11, 2012

Triplet repeats in transcripts: structural insights into RNA toxicity

Paulina Galka-Marciniak, Martyna O. Urbanek, Wlodzimierz J. Krzyzosiak

Page range: 1299-1315

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Abstract

Tandem repeats of various trinucleotide motifs are frequent entities in transcripts, and RNA structures formed by these sequences depend on the motif type and number of reiterations. The functions performed by normal triplet repeats in transcripts are poorly understood, but abnormally expanded repeats of certain types trigger pathogenesis in several human genetic disorders known as the triplet repeat expansion diseases (TREDs). The diseases caused by expanded non-coding CUG and CGG repeats in transcripts include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome. Another group of disorders in which transcripts containing translated CAG repeats play an auxiliary role in pathogenesis include Huntington’s disease and several spinocerebellar ataxias. In this review, we gathered existing knowledge regarding the structural features of triplet repeats in transcripts and discussed this in the context of various pathogenic mechanisms assigned to toxic RNA repeats. These mechanisms include aberrant alternative splicing, the inhibition of nuclear transport and export, induction of the innate immune response, alteration of a microRNA biogenesis pathway and abnormal activation of an RNA interference pathway. We also provide ideas for future investigations to reveal further mechanisms of pathogenesis directly triggered by mutant RNA repeats in TREDs.

Open Access October 11, 2012

Intronic hammerhead ribozymes in mRNA biogenesis

Inmaculada García-Robles, Jesús Sánchez-Navarro, Marcos de la Peña

Page range: 1317-1326

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Abstract

Small self-cleaving ribozymes are a group of natural RNAs that are capable of catalyzing their own and sequence-specific endonucleolytic cleavage. One of the most studied members is the hammerhead ribozyme (HHR), a catalytic RNA originally discovered in subviral plant pathogens but recently shown to reside in a myriad of genomes along the tree of life. In eukaryotes, most of the genomic HHRs seem to be related to short interspersed retroelements, with the main exception of a group of strikingly conserved ribozymes found in the genomes of all amniotes (reptiles, birds and mammals). These amniota HHRs occur in the introns of a few specific genes, and clearly point to a preserved biological role during pre-mRNA biosynthesis. More specifically, bioinformatic analysis suggests that these intronic ribozymes could offer a new form of splicing regulation of the mRNA of higher vertebrates. We review here the latest advances in the discovery and biological characterization of intronic HHRs of vertebrates, including new conserved examples in the genomes of the primitive turtle and coelacanth fish.

October 11, 2012

Interaction between natural compounds and human topoisomerase I

Silvia Castelli, Andrea Coletta, Ilda D’Annessa, Paola Fiorani, Cinzia Tesauro, Alessandro Desideri

Page range: 1327-1340

Abstract

Eukaryotic topoisomerase I (Top1) is a monomeric enzyme that catalyzes the relaxation of supercoiled DNA during important processes including DNA replication, transcription, recombination and chromosome condensation. Human Top1 I is of significant medical interest since it is the unique cellular target of camptothecin (CPT), a plant alkaloid that rapidly blocks both DNA and RNA synthesis. In this review, together with CPT, we point out the interaction between human Top1 and some natural compounds, such us terpenoids, flavonoids, stilbenes and fatty acids. The drugs can interact with the enzyme at different levels perturbing the binding, cleavage, rotation or religation processes. Here we focus on different assays that can be used to identify the catalytic step of the enzyme inhibited by different natural compounds.

Research Articles/Short Communications

Protein Structure and Function

October 11, 2012

β-Barrel scaffolds for the grafting of extracellular loops from G-protein-coupled receptors

Reto Walser, Jörg H. Kleinschmidt, Arne Skerra, Oliver Zerbe

Page range: 1341-1355

Abstract

Owing to the difficulties in production and purification of G-protein-coupled receptors (GPCRs), relatively little structural information is available about this class of receptors. Here we aim at developing small chimeric proteins, displaying the extracellular ligand-binding motifs of a human GPCR, the Y receptor. This allows the study of ligand-receptor interactions in simplified systems. We present comprehensive information on the use of transmembrane (OmpA) and soluble (Blc) β-barrel scaffolds. Whereas Blc appeared to be not fully compatible with our approach, owing to problems with refolding of the hybrid constructs, loop-grafted versions of OmpA delivered encouraging results. Previously, we described a chimeric construct based on OmpA displaying all three extracellular Y1 receptor loops in different topologies and showing moderate affinity to one of the natural ligands. Now, we present detailed data on the interaction of these constructs with several Y receptor ligands along with data on new constructs. Our findings suggest a common binding mode for all ligands, which is mediated through the C-terminal residues of the peptide ligand, supporting the functional validity of these hybrid receptors. The observed binding affinities, however, are well below those observed for the natural receptors, clearly indicating limitations in mimicking the natural systems.

Membranes, Lipids, Glycobiology

October 11, 2012

The GlycanBuilder and GlycoWorkbench glycoinformatics tools: updates and new developments

David Damerell, Alessio Ceroni, Kai Maass, Rene Ranzinger, Anne Dell, Stuart M. Haslam

Page range: 1357-1362

Abstract

During the EUROCarbDB project our group developed the GlycanBuilder and GlycoWorkbench glycoinformatics tools. This short communication summarizes the capabilities of these two tools and updates which have been made since the original publications in 2007 and 2008. GlycanBuilder is a tool that allows for the fast and intuitive drawing of glycan structures; this tool can be used standalone, embedded in web pages and can also be integrated into other programs. GlycoWorkbench has been designed to semi-automatically annotate glycomics data. This tool can be used to annotate mass spectrometry (MS) and MS/MS spectra of free oligosaccharides, N and O-linked glycans, GAGs ( g lycos a mino g lycans) and glycolipids, as well as MS spectra of glycoproteins.

About this journal

Objective
Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences.

Topics

general biochemistry
pathobiochemistry
structural biology
molecular and cellular biology
genetics and epigenetics
molecular medicine
cancer research
virology
immunology
plant molecular biology and biochemistry
novel experimental methodologies

Article formats
Research Articles, Short Communications, Reviews and Minireviews
Reviews are published by invitation only, but suggestions to the Editor-in-Chief are welcome.

The journal is associated with the German Society for Biochemistry and Molecular Biology (GBM).