TMBETA-GENOME: database for annotated β-barrel membrane proteins in genomic sequences

We have developed the database, TMBETA-GENOME, for annotated β-barrel membrane proteins in genomic sequences using statistical methods and machine learning algorithms. The statistical methods are based on amino acid composition, reside pair preference and motifs. In machine learning techniques, the combination of amino acid and dipeptide compositions has been used as main attributes. In addition, annotations have been made using the criterion based on the identification of β-barrel membrane proteins and exclusion of globular and transmembrane helical proteins. A web interface has been developed for identifying the annotated β-barrel membrane proteins in all known genomes. The users have the feasibility of selecting the genome from the three kingdoms of life, archaea, bacteria and eukaryote, and five different methods. Further, the statistics for all genomes have been provided along with the links to different algorithms and related databases. It is freely available at

TMBETA-NET: discrimination and prediction of membrane spanning β-strands in outer membrane proteins

We have developed a web-server, TMBETA-NET for discriminating outer membrane proteins and predicting their membrane spanning β-strand segments. The amino acid compositions of globular and outer membrane proteins have been systematically analyzed and a statistical method has been proposed for discriminating outer membrane proteins. The prediction of membrane spanning segments is mainly based on feed forward neural network and refined with β-strand length. Our program takes the amino acid sequence as input and displays the type of the protein along with membrane-spanning β-strand segments as a stretch of highlighted amino acid residues. Further, the probability of residues to be in transmembrane β-strand has been provided with a coloring scheme. We observed that outer membrane proteins were discriminated with an accuracy of 89% and their membrane spanning β-strand segments at an accuracy of 73% just from amino acid sequence information. The prediction server is available at

transFold: a web server for predicting the structure and residue contacts of transmembrane beta-barrels

Transmembrane β-barrel (TMB) proteins are embedded in the outer membrane of Gram-negative bacteria, mitochondria and chloroplasts. The cellular location and functional diversity of β-barrel outer membrane proteins makes them an important protein class. At the present time, very few non-homologous TMB structures have been determined by X-ray diffraction because of the experimental difficulty encountered in crystallizing transmembrane (TM) proteins. The transFold web server uses pairwise inter-strand residue statistical potentials derived from globular (non-outer-membrane) proteins to predict the supersecondary structure of TMB. Unlike all previous approaches, transFold does not use machine learning methods such as hidden Markov models or neural networks; instead, transFold employs multi-tape S-attribute grammars to describe all potential conformations, and then applies dynamic programming to determine the global minimum energy supersecondary structure. The transFold web server not only predicts secondary structure and TMB topology, but is the only method which additionally predicts the side-chain orientation of transmembrane β-strand residues, inter-strand residue contacts and TM β-strand inclination with respect to the membrane. The program transFold currently outperforms all other methods for accuracy of β-barrel structure prediction. Available at

Outer membrane proteins can be simply identified using secondary structure element alignment

<p>Abstract</p> <p>Background</p> <p>Outer membrane proteins (OMPs) are frequently found in the outer membranes of gram-negative bacteria, mitochondria and chloroplasts and have been found to play diverse functional roles. Computational discrimination of OMPs from globular proteins and other types of membrane proteins is helpful to accelerate new genome annotation and drug discovery.</p> <p>Results</p> <p>Based on the observation that almost all OMPs consist of antiparallel β-strands in a barrel shape and that their secondary structure arrangements differ from those of other types of proteins, we propose a simple method called SSEA-OMP to identify OMPs using secondary structure element alignment. Through intensive benchmark experiments, the proposed SSEA-OMP method is better than some well-established OMP detection methods.</p> <p>Conclusions</p> <p>The major advantage of SSEA-OMP is its good prediction performance considering its simplicity. The web server implements the method is freely accessible at <url>http://protein.cau.edu.cn/SSEA-OMP/index.html</url>.</p

In silico local structure approach: A case study on Outer Membrane Proteins.

International audienceThe detection of Outer Membrane Proteins (OMP) in whole genomes is an actual question, their sequence characteristics have thus been intensively studied. This class of protein displays a common beta-barrel architecture, formed by adjacent antiparallel strands. However, due to the lack of available structures, few structural studies have been made on this class of proteins. Here we propose a novel OMP local structure investigation, based on a structural alphabet approach, i.e., the decomposition of 3D structures using a library of four-residue protein fragments. The optimal decomposition of structures using hidden Markov model results in a specific structural alphabet of 20 fragments, six of them dedicated to the decomposition of beta-strands. This optimal alphabet, called SA20-OMP, is analyzed in details, in terms of local structures and transitions between fragments. It highlights a particular and strong organization of beta-strands as series of regular canonical structural fragments. The comparison with alphabets learned on globular structures indicates that the internal organization of OMP structures is more constrained than in globular structures. The analysis of OMP structures using SA20-OMP reveals some recurrent structural patterns. The preferred location of fragments in the distinct regions of the membrane is investigated. The study of pairwise specificity of fragments reveals that some contacts between structural fragments in beta-sheets are clearly favored whereas others are avoided. This contact specificity is stronger in OMP than in globular structures. Moreover, SA20-OMP also captured sequential information. This can be integrated in a scoring function for structural model ranking with very promising results. Proteins 2007. (c) 2007 Wiley-Liss, Inc

Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome

The bacterial cell-envelope consists of a complex arrangement of lipids, proteins and carbohydrates that serves as the interface between a microorganism and its environment or, with pathogens, a human host. Escherichia coli has long been investigated as a leading model system to elucidate the fundamental mechanisms underlying microbial cell-envelope biology. This includes extensive descriptions of the molecular identities, biochemical activities and evolutionary trajectories of integral transmembrane proteins, many of which play critical roles in infectious disease and antibiotic resistance. Strikingly, however, only half of the c. 1200 putative cell-envelope-related proteins of E. coli currently have experimentally attributed functions, indicating an opportunity for discovery. In this review, we summarize the state of the art of computational and proteomic approaches for determining the components of the E. coli cell-envelope proteome, as well as exploring the physical and functional interactions that underlie its biogenesis and functionality. We also provide a comprehensive comparative benchmarking analysis on the performance of different bioinformatic and proteomic methods commonly used to determine the subcellular localization of bacterial proteins

ptOmp85 – ein Toc75-Homolog in der dritten Plastidenmembran von Phaeodactylum tricornutum

Chromalveolaten sind eine hochdiverse Gruppe von Protisten, die als gemeinsames Merkmal eine sogenannte komplexe Plastide tragen. Diese ist das Resultat einer sekundären Endocytobiose zwischen einer eukaryoten Wirtszelle und einer Rhodophyte. Die komplexe Plastide ist, anders als die primären Plastiden der Archaeplastida, i. d. R von vier Membranen umgeben (eine Ausnahme bilden die Plastiden der Peridinin-haltigen Dinoflagellaten mit nur drei Membranen). Wie auch bei den Archaeplastida ist ein Großteil der plastidären Proteine von Chromalveolaten auf dem Kerngenom des Wirtes codiert, und muss daher posttranslational aus dem Cytosol importiert werden. Proteine des Plastidenstromas müssen also vier Membranen passieren. Während für drei der vier Membranen bereits putative Translokatoren beschrieben werden konnten, war das Translokon der drittäußersten Membran bislang völlig unbekannt. Diese Membran ist der äußeren Membran primärer Plastiden homolog, ein entsprechendes Toc-Translokon konnte allerdings bislang nicht identifiziert werden. Im Rahmen dieser Arbeit wurde ein kürzlich identifiziertes putatives Omp85-Protein der Diatomee Phaeodactylum tricornutum erstmals eingehend analysiert und charakterisiert. Das Protein, ptOmp85, konnte eindeutig der Familie der Omp85- Proteine zugeordnet werden. Innerhalb der Familie weist es die die nächsten Verwandtschaftsbeziehungen zum Toc75-Homolog der freilebenden Rotalge Cyanidioschyzon merolae auf. Es konnte nachgewiesen werden, dass ptOmp85 ein integrales Protein der drittäußersten Membran der komplexen Plastide ist. Darüber hinaus konnte gezeigt werden, dass ptOmp85 intraorganellär einem zu Toc75 homologen. Zielsteuerungsmechanismus unterliegt. Die Analyse der elektrophysiolgischen Eigenschaften der Membranpore von ptOmp85 zeigte eindeutige Ähnlichkeiten zu den Poreneigenschaften von Toc75-artigen, nicht aber zu denen von Sam50-artigen Omp85-Proteinen. Diese aufgedeckten Charakteristika implizieren, dass es sich bei ptOm85 tatsächlich um das Proteintranslokon der drittäußersten Plastidenmembran von Chromalveolaten handelt. Die Ergebnisse dieser Arbeit tragen somit grundlegend zum Verständnis des Proteinimports in die komplexen Plastiden dieser Protistengruppe bei