Structural analysis of hubs in human NR-RTK network

<p>Abstract</p> <p>Background</p> <p>Currently a huge amount of protein-protein interaction data is available therefore extracting meaningful ones are a challenging task. In a protein-protein interaction network, hubs are considered as key proteins maintaining function and stability of the network. Therefore, studying protein-protein complexes from a structural perspective provides valuable information for predicted interactions.</p> <p>Results</p> <p>In this study, we have predicted by comparative modelling and docking methods protein-protein complexes of hubs of human NR-RTK network inferred from our earlier study. We found that some interactions are mutually excluded while others could occur simultaneously. This study revealed by structural analysis the key role played by Estrogen receptor (ESR1) in mediating the signal transduction between human Receptor Tyrosine kinases (RTKs) and nuclear receptors (NRs).</p> <p>Conclusions</p> <p>Although the methods require human intervention and judgment, they can identify the interactions that could occur together or ones that are mutually exclusive. This adds a fourth dimension to interaction network, that of time, and can assist in obtaining concrete predictions consistent with experiments.</p> <p>Open peer review</p> <p>This article was reviewed by Dr. Anthony Almudevar, Prof. James Faeder and Prof. Eugene Koonin. For the full reviews, please go to the Reviewers' comments.</p

Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors

<p>Abstract</p> <p>Background</p> <p>Nuclear receptors (NRs) and Receptor tyrosine kinases (RTKs) are essential proteins in many cellular processes and sequence variations in their genes have been reported to be involved in many diseases including cancer. Although crosstalk between RTK and NR signalling and their contribution to the development of endocrine regulated cancers have been areas of intense investigation, the direct coupling of their signalling pathways remains elusive. In our understanding of the role and function of nuclear receptors on the cell membrane the interactions between nuclear receptors and tyrosine kinase receptors deserve further attention.</p> <p>Results</p> <p>We constructed a human signalling network containing nuclear receptors and tyrosine kinase receptors that identified a network topology involving eleven highly connected hubs.</p> <p>We further developed an integrated knowledge database, denominated NR-RTK database dedicated to human RTKs and NRs and their vertebrate orthologs and their interactions. These interactions were inferred using computational tools and those supported by literature evidence are indicated. NR-RTK database contains links to other relevant resources and includes data on receptor ligands. It aims to provide a comprehensive interaction map that identifies complex dynamics and potential crosstalk involved.</p> <p>Availability: NR-RTK database is accessible at <url>http://www.bioinfo-cbs.org/NR-RTK/</url></p> <p>Conclusions</p> <p>We infer that the NR-RTK interaction network is scale-free topology. We also uncovered the key receptors mediating the signal transduction between these two types of receptors. Furthermore, NR-RTK database is expected to be useful for researchers working on various aspects of the molecular basis of signal transduction by RTKs and NRs.</p> <p>Reviewers</p> <p>This article was reviewed by Professor Paul Harrison (nominated by Dr. Mark Gerstein), Dr. Arcady Mushegian and Dr. Anthony Almudevar.</p

Exploring disorder in the human charged biased proteins

<p>A considerable interest has been put in the identification of biased regions in proteins. These regions are frequently associated with a structural role in the cell and particularly with protein disorder. Here, we have investigated the intrinsically disordered regions (IDRs) in the human charged biased proteins identified in our earlier work. We found that 65% of charged biased proteins contained significant IDRs involved particularly in DNA and RNA binding. Also, we have observed that these proteins are well conserved in metazoans and more particularly in mammalian. In addition, the IDRs are located largely in N-terminal, C-terminal sequence flanking the functional domains (FD) and slightly less in (FD) itself. Our work also supports the association between protein disorder and protein–protein/DNA interaction. An example will be described.</p

Discovery and Potential of SNP Markers in Characterization of Tunisian Olive Germplasm

Single Nucelotide Polymorphisms (SNPs) have become the most widely used markers in many current genetic applications. Here we report the discovery of nine new SNPs in olives by direct partial sequencing of two genes (OEX and OEW) in sixteen Tunisian cultivars. The SNP markers were then used to genotype 24 olive cultivars and assess the level of genetic diversity. Power of discrimination of SNP markers was then compared to that of microsatellites (SSRs). A combination of SSR and SNP markers was finally proposed that can be used for cultivars identification in juvenile step or for oil traceability