Evolutionary flexibility of protein complexes

<p>Abstract</p> <p>Background</p> <p>Proteins play a key role in cellular life. They do not act alone but are organised in complexes. Throughout the life of a cell, complexes are dynamic in their composition due to attachments and shared components. Experimental and computational evidence indicate that consecutive addition and secondary losses of components played a major role in the evolution of some complexes, mostly without affecting the core function. Here, we analysed in a large scale approach whether this flexibility in evolution is only limited to a distinct number of complexes or represents a more general trend.</p> <p>Results</p> <p>Focussing on human protein complexes, we based our analysis on a manually curated dataset from HPRD. In total, 1,060 complexes with 6,136 proteins from 2,187 unique genes were considered. We computed interologs in 25 different species and predicted the composition of complexes. Over the analysed species, the composition of most complexes was highly flexible and only 25% of all genes were never lost. Even if one component was lost at a particular point in time, the fraction of observed second, independent losses of additional components was high (75% of all complexes affected). Still, loss of whole complexes happened rarely. This biological signal deviated significantly from random models. We exemplified this trend on the anaphase promoting complex (APC) where a core is highly conserved throughout all metazoans, but flexibility in certain components is observable.</p> <p>Conclusion</p> <p>Consecutive additions and losses of distinct units is a fundamental process in the evolution of protein complexes. These evolutionary events affecting genes coding for units in human protein complexes showed a significantly different phylogenetic pattern compared to randomly selected genes. Determination of taxon specific attachments or losses might be linked to specific cellular or morphological features. Thus, protein complexes contain not only structural and functional, but also evolutionary cores.</p

Partially-supervised protein subclass discovery with simultaneous annotation of functional residues

<p>Abstract</p> <p>Background</p> <p>The study of functional subfamilies of protein domain families and the identification of the residues which determine substrate specificity is an important question in the analysis of protein domains. One way to address this question is the use of clustering methods for protein sequence data and approaches to predict functional residues based on such clusterings. The locations of putative functional residues in known protein structures provide insights into how different substrate specificities are reflected on the protein structure level.</p> <p>Results</p> <p>We have developed an extension of the <it>context-specific independence </it>mixture model clustering framework which allows for the integration of experimental data. As these are usually known only for a few proteins, our algorithm implements a partially-supervised learning approach. We discover domain subfamilies and predict functional residues for four protein domain families: phosphatases, pyridoxal dependent decarboxylases, WW and SH3 domains to demonstrate the usefulness of our approach.</p> <p>Conclusion</p> <p>The partially-supervised clustering revealed biologically meaningful subfamilies even for highly heterogeneous domains and the predicted functional residues provide insights into the basis of the different substrate specificities.</p

HMM Logos for visualization of protein families

BACKGROUND: Profile Hidden Markov Models (pHMMs) are a widely used tool for protein family research. Up to now, however, there exists no method to visualize all of their central aspects graphically in an intuitively understandable way. RESULTS: We present a visualization method that incorporates both emission and transition probabilities of the pHMM, thus extending sequence logos introduced by Schneider and Stephens. For each emitting state of the pHMM, we display a stack of letters. The stack height is determined by the deviation of the position's letter emission frequencies from the background frequencies. The stack width visualizes both the probability of reaching the state (the hitting probability) and the expected number of letters the state emits during a pass through the model (the state's expected contribution). A web interface offering online creation of HMM Logos and the corresponding source code can be found at the Logos web server of the Max Planck Institute for Molecular Genetics . CONCLUSIONS: We demonstrate that HMM Logos can be a useful tool for the biologist: We use them to highlight differences between two homologous subfamilies of GTPases, Rab and Ras, and we show that they are able to indicate structural elements of Ras

Variation in structural location and amino acid conservation of functional sites in protein domain families

BACKGROUND: The functional sites of a protein present important information for determining its cellular function and are fundamental in drug design. Accordingly, accurate methods for the prediction of functional sites are of immense value. Most available methods are based on a set of homologous sequences and structural or evolutionary information, and assume that functional sites are more conserved than the average. In the analysis presented here, we have investigated the conservation of location and type of amino acids at functional sites, and compared the behaviour of functional sites between different protein domains. RESULTS: Functional sites were extracted from experimentally determined structural complexes from the Protein Data Bank harbouring a conserved protein domain from the SMART database. In general, functional (i.e. interacting) sites whose location is more highly conserved are also more conserved in their type of amino acid. However, even highly conserved functional sites can present a wide spectrum of amino acids. The degree of conservation strongly depends on the function of the protein domain and ranges from highly conserved in location and amino acid to very variable. Differentiation by binding partner shows that ion binding sites tend to be more conserved than functional sites binding peptides or nucleotides. CONCLUSION: The results gained by this analysis will help improve the accuracy of functional site prediction and facilitate the characterization of unknown protein sequences

Regulierung der Weißen Fliege im Kohlanbau durch den kombinierten Einsatz von Kulturschutznetzen und Nützlingen – Erste Ergebnisse des BÖL-Projekts

The cabbage whitefly, Aleyrodes proletella, has gradually developed into a key pest, affecting the quality of organic Brassica vegetables. Netting may provide partial control of the cabbage whitefly. In the ongoing project mechanical control methods using the barrier effect of netting and biological control methods with naturally occurring whitefly antagonists, namely the predatory ladybeetle Clitostethus arcuatus and the larval parasitoid Encarsia tricolor, are combined and their efficiency tested in small-scale field experiments. During the first year, adverse weather conditions affected the study. However, first results indicate, that even under relatively low host densities the parasitation by E. tricolor was enhanced after their release inside the nets, in comparison to corresponding controls with nets only. C. arcuatus adults were recovered up to 60 days after their release, although progeny was not observed throughout the vegetation period. Application of netting reduced whitefly larvae and puparia by more than 70%