3D-cardiomics: A spatial transcriptional atlas of the mammalian heart.

Understanding the spatial gene expression and regulation in the heart is key to uncovering its developmental and physiological processes, during homeostasis and disease. Numerous techniques exist to gain gene expression and regulation information in organs such as the heart, but few utilize intuitive true-to-life three-dimensional representations to analyze and visualise results. Here we combined transcriptomics with 3D-modelling to interrogate spatial gene expression in the mammalian heart.

The three-dimensional structure of the extracellular adhesion domain of the sialic acid-binding adhesin SabA from Helicobacter pylori.

The gastric pathogen Helicobacter pylori is a major cause of acute chronic gastritis and the development of stomach and duodenal ulcers. Chronic infection furthermore predisposes to the development of gastric cancer. Crucial to H.

A molecular switch governs the interaction between the human complement protease C1s and its substrate, complement C4.

The complement system is an ancient innate immune defense pathway that plays a front line role in eliminating microbial pathogens. Recognition of foreign targets by antibodies drives sequential activation of two serine proteases, C1r and C1s, which reside within the complement Component 1 (C1) complex. Active C1s propagates the immune response through its ability to bind and cleave the effector molecule complement Component 4 (C4).

Inmembrane, a bioinformatic workflow for annotation of bacterial cell-surface proteomes.

Background: The annotation of surface exposed bacterial membrane proteins is an important step in interpretation and validation of proteomic experiments. In particular, proteins detected by cell surface protease shaving experiments can indicate exposed regions of membrane proteins that may contain antigenic determinants or constitute vaccine targets in pathogenic bacteria.

Results: Inmembrane is a tool to predict the membrane proteins with surface-exposed regions of polypeptide in sets of bacterial protein sequences.

PROSPER: an integrated feature-based tool for predicting protease substrate cleavage sites.

The ability to catalytically cleave protein substrates after synthesis is fundamental for all forms of life. Accordingly, site-specific proteolysis is one of the most important post-translational modifications. The key to understanding the physiological role of a protease is to identify its natural substrate(s).

Dynamic association of BAM complex modules includes surface exposure of the lipoprotein BamC.

The β-barrel assembly machinery (BAM) complex drives the assembly of β-barrel proteins into the outer membrane of gram-negative bacteria. It is composed of five subunits: BamA, BamB, BamC, BamD, and BamE. We find that the BAM complex isolated from the outer membrane of Escherichia coli consists of a core complex of BamA:B:C:D:E and, in addition, a BamA:B module and a BamC:D module.

The evolution of new lipoprotein subunits of the bacterial outer membrane BAM complex.

The β-barrel assembly machine (BAM) complex is an essential feature of all bacteria with an outer membrane. The core subunit of the BAM complex is BamA and, in Escherichia coli, four lipoprotein subunits: BamB, BamC, BamD and BamE, also function in the BAM complex. Hidden Markov model analysis was used to comprehensively assess the distribution of subunits of the BAM lipoproteins across all subclasses of proteobacteria.

Discovery of an archetypal protein transport system in bacterial outer membranes.

Bacteria have mechanisms to export proteins for diverse purposes, including colonization of hosts and pathogenesis. A small number of archetypal bacterial secretion machines have been found in several groups of bacteria and mediate a fundamentally distinct secretion process. Perhaps erroneously, proteins called 'autotransporters' have long been thought to be one of these protein secretion systems.

Mitochondrial preprotein translocase of trypanosomatids has a bacterial origin.

Mitochondria are found in all eukaryotic cells and derive from a bacterial endosymbiont [1, 2]. The evolution of a protein import system was a prerequisite for the conversion of the endosymbiont into a true organelle. Tom40, the essential component of the protein translocase of the outer membrane, is conserved in mitochondria of almost all eukaryotes but lacks bacterial orthologs [3-6].

The core components of organelle biogenesis and membrane transport in the hydrogenosomes of Trichomonas vaginalis.

Trichomonas vaginalis is a parasitic protist of the Excavata group. It contains an anaerobic form of mitochondria called hydrogenosomes, which produce hydrogen and ATP; the majority of mitochondrial pathways and the organellar genome were lost during the mitochondrion-to-hydrogenosome transition. Consequently, all hydrogenosomal proteins are encoded in the nucleus and imported into the organelles.

The minimal proteome in the reduced mitochondrion of the parasitic protist Giardia intestinalis.

The mitosomes of Giardia intestinalis are thought to be mitochondria highly-reduced in response to the oxygen-poor niche. We performed a quantitative proteomic assessment of Giardia mitosomes to increase understanding of the function and evolutionary origin of these enigmatic organelles. Mitosome-enriched fractions were obtained from cell homogenate using Optiprep gradient centrifugation.

Recognition of mitochondrial targeting sequences by the import receptors Tom20 and Tom22.

The Tom20 and Tom22 receptor subunits of the TOM (translocase of the outer mitochondrial membrane) complex recognize N-terminal presequences of proteins that are to be imported into the mitochondrion. In plants, Tom20 is C-terminally anchored in the mitochondrial membrane, whereas Tom20 is N-terminally anchored in animals and fungi. Furthermore, the cytosolic domain of Tom22 in plants is smaller than its animal/fungal counterpart and contains fewer acidic residues.

The reducible complexity of a mitochondrial molecular machine.

Molecular machines drive essential biological processes, with the component parts of these machines each contributing a partial function or structural element. Mitochondria are organelles of eukaryotic cells, and depend for their biogenesis on a set of molecular machines for protein transport. How these molecular machines evolved is a fundamental question.

Protein secretion and outer membrane assembly in Alphaproteobacteria.

The assembly of beta-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of beta-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating beta-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent.

Structure, topology and function of the translocase of the outer membrane of mitochondria.

Proteins destined for the mitochondria required the evolution of specific and efficient molecular machinery for protein import. The subunits of the import translocases of the inner membrane (TIM) appear homologous and conserved amongst species, however the components of the translocase of the outer membrane (TOM) show extensive differences between species. Recently, bioinformatic and structural analysis of Tom20, an important receptor subunit of the TOM complex, suggests that this protein complex arose from different ancestors for plants compared to animals and fungi, but has subsequently converged to provide similar functions and analogous structures.

The transmembrane segment of Tom20 is recognized by Mim1 for docking to the mitochondrial TOM complex.

Mitochondria cannot be made de novo. Mitochondrial biogenesis requires that up to 1000 proteins are imported into mitochondria, and the protein import pathway relies on hetero-oligomeric translocase complexes in both the inner and outer mitochondrial membranes. The translocase in the outer membrane, the TOM complex, is composed of a core complex formed from the beta-barrel channel Tom40 and additional subunits each with single, alpha-helical transmembrane segments.

Conserved motifs reveal details of ancestry and structure in the small TIM chaperones of the mitochondrial intermembrane space.

The mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. The small translocase of the inner mitochondrial membranes (TIMs) are a group of approximately 10 kDa proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. In yeast, there are 5 small TIM proteins: Tim8, Tim9, Tim10, Tim12, and Tim13, with equivalent proteins reported in humans.

Convergent evolution of receptors for protein import into mitochondria.

Background: Mitochondria evolved from intracellular bacterial symbionts. Establishing mitochondria as organelles required a molecular machine to import proteins across the mitochondrial outer membrane. This machinery, the TOM complex, is composed of at least seven component parts, and its creation and evolution represented a sizeable challenge.

Protein targeting: entropy, energetics and modular machines.

New light is being shed on the mechanism of protein import into mitochondria. The inner membrane translocase can switch between modes of translocation, and assists what might be an entropic device to drive the initial entry of substrate proteins across the outer membrane.