Hedvig Hegyi

The SBASE Protein Domain Library, Release 4.0: A Collection of Annotated Protein Sequence Segments

SBASE 4.0 is the fourth release of SBASE, a collection of annotated protein domain sequences that represent various structural, functional, ligand binding and topogenic segments of proteins. SBASE was designed to facilitate the detection of functional homologies and can be searched with standard database search tools, such as FASTA and BLAST3. The present release contains 61 137 entries provided with standardized names and cross-referenced to all major protein, nucleic acid and sequence pattern collections. The entries are clustered into 13 155 groups in order to facilitate detection of distant similarities. SBASE 4.0 is freely available by anonymous ftp file transfer from ftp.icgeb.trieste.it. Individual records can be retrieved with the gopher server at icgeb.trieste.it and with a World Wide Web server at http://www.icgeb.trieste.it. Automated searching of SBASE with BLAST can be carried out with the electronic mail server sbase@icgeb.trieste.it, which now also provides a graphic representation of the homologies. A related mail server, domain@hubi.abc.hu, assigns SBASE domain homologies on the basis of SWISS-PROT searches.

On the Classification and Evolution of Protein Modules

Our efforts to classify the functional units of many proteins, the modules, are reviewed. The data from the sequencing projects for various model organisms are extremely helpful in deducing the evolution of proteins and modules. For example, a dramatic increase of modular proteins can be observed from yeast to C. elegans in accordance with new protein functions that had to be introduced in multicellular organisms. Our sequence characterization of modules relies on sensitive similarity search algorithms and the collection of multiple sequence alignments for each module. To trace the evolution of modules and to further automate the classification, we have developed a sequence and a module alerting system that checks newly arriving sequence data for the presence of already classified modules. Using these systems, we were able to identify an unexpected similarity between extracellular C1Q modules with bacterial proteins.

Enhancer-promoter interaction facilitated by transiently forming G-quadruplexes

G-quadruplexes are guanine-rich nucleic acid sequences capable of forming a four-stranded structure through Hoogsteen hydrogen bonding. G-quadruplexes are highly concentrated near promoters and transcription start sites suggesting a role in gene regulation. They are less often found on the template than non-template strand where they either inhibit or enhance transcription, respectively. However, their potential role in enhancers and other distal regulatory elements has not been assessed yet. Here we show that DNAse hypersensitive (DHS) cis-regulatory elements are also enriched in Gs and their G-content correlate with that of their respective promoters. Besides local G4s, the distal cis regions may form G-quadruplexes together with the promoters, each contributing half a G4. This model is supported more for the non-template strand and we hypothesised that the G4 forming capability of the promoter and the enhancer non-template strand could facilitate their binding together and making the DHS regions accessible for the transcription factory.

The domain-server: direct prediction of protein domain-homologies from BLAST search.

RESULTS A WWW server for protein domain homology prediction, based on BLAST search and a simple data-mining algorithm (Hegyi,H. and Pongor,S. (1993) Comput. Appl. Biosci., 9, 371-372), was constructed providing a tabulated list and a graphic plot of similarities. AVAILABILITY http://www.icgeb.trieste.it/domain. Mirror site is available at http://sbase.abc.hu/domain. A standalone programme will be available on request. SUPPLEMENTARY INFORMATION A series of help files is available at the above addresses.

A novel aspect of the information content of viroids

Viroids were found to exhibit a structural periodicity characterized by repeat units of a length of 11 or 12 (potato spindle tuber viroid group and coconut cadang-cadang viroid), 60 (apple scar skin viroid) and 80 (avocado sunblotch viroid) nucleotide residues, respectively. It is suggested that structural periodicity of viroids is an indication of their protein-binding ability.

The Sequence Alerting Server—a new WEB server

UNLABELLED A Sequence Alerting Server with a WWW interface is described which informs users with query sequences in database searches about new entries in protein databases related to their query. AVAILABILITY The server address is http://www.bork.embl-heidelberg.de/alerting/.