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      AMYPdb: A database dedicated to amyloid precursor proteins

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      1 , 1 , 1 ,
      BMC Bioinformatics
      BioMed Central

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          Abstract

          Background

          Misfolding and aggregation of proteins into ordered fibrillar structures is associated with a number of severe pathologies, including Alzheimer's disease, prion diseases, and type II diabetes. The rapid accumulation of knowledge about the sequences and structures of these proteins allows using of in silico methods to investigate the molecular mechanisms of their abnormal conformational changes and assembly. However, such an approach requires the collection of accurate data, which are inconveniently dispersed among several generalist databases.

          Results

          We therefore created a free online knowledge database (AMYPdb) dedicated to amyloid precursor proteins and we have performed large scale sequence analysis of the included data. Currently, AMYPdb integrates data on 31 families, including 1,705 proteins from nearly 600 organisms. It displays links to more than 2,300 bibliographic references and 1,200 3D-structures. A Wiki system is available to insert data into the database, providing a sharing and collaboration environment. We generated and analyzed 3,621 amino acid sequence patterns, reporting highly specific patterns for each amyloid family, along with patterns likely to be involved in protein misfolding and aggregation.

          Conclusion

          AMYPdb is a comprehensive online database aiming at the centralization of bioinformatic data regarding all amyloid proteins and their precursors. Our sequence pattern discovery and analysis approach unveiled protein regions of significant interest. AMYPdb is freely accessible [ 1].

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          Most cited references38

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          The Universal Protein Resource (UniProt): an expanding universe of protein information

          The Universal Protein Resource (UniProt) provides a central resource on protein sequences and functional annotation with three database components, each addressing a key need in protein bioinformatics. The UniProt Knowledgebase (UniProtKB), comprising the manually annotated UniProtKB/Swiss-Prot section and the automatically annotated UniProtKB/TrEMBL section, is the preeminent storehouse of protein annotation. The extensive cross-references, functional and feature annotations and literature-based evidence attribution enable scientists to analyse proteins and query across databases. The UniProt Reference Clusters (UniRef) speed similarity searches via sequence space compression by merging sequences that are 100% (UniRef100), 90% (UniRef90) or 50% (UniRef50) identical. Finally, the UniProt Archive (UniParc) stores all publicly available protein sequences, containing the history of sequence data with links to the source databases. UniProt databases continue to grow in size and in availability of information. Recent and upcoming changes to database contents, formats, controlled vocabularies and services are described. New download availability includes all major releases of UniProtKB, sequence collections by taxonomic division and complete proteomes. A bibliography mapping service has been added, and an ID mapping service will be available soon. UniProt databases can be accessed online at or downloaded at .
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            Common core structure of amyloid fibrils by synchrotron X-ray diffraction.

            Tissue deposition of normally soluble proteins as insoluble amyloid fibrils is associated with serious diseases including the systemic amyloidoses, maturity onset diabetes, Alzheimer's disease and transmissible spongiform encephalopathy. Although the precursor proteins in different diseases do not share sequence homology or related native structure, the morphology and properties of all amyloid fibrils are remarkably similar. Using intense synchrotron sources we observed that six different ex vivo amyloid fibrils and two synthetic fibril preparations all gave similar high-resolution X-ray fibre diffraction patterns, consistent with a helical array of beta-sheets parallel to the fibre long axis, with the strands perpendicular to this axis. This confirms that amyloid fibrils comprise a structural superfamily and share a common protofilament substructure, irrespective of the nature of their precursor proteins. Copyright 1997 Academic Press Limited.
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              The PROSITE database

              The PROSITE database consists of a large collection of biologically meaningful signatures that are described as patterns or profiles. Each signature is linked to a documentation that provides useful biological information on the protein family, domain or functional site identified by the signature. The PROSITE database is now complemented by a series of rules that can give more precise information about specific residues. During the last 2 years, the documentation and the ScanProsite web pages were redesigned to add more functionalities. The latest version of PROSITE (release 19.11 of September 27, 2005) contains 1329 patterns and 552 profile entries. Over the past 2 years more than 200 domains have been added, and now 52% of UniProtKB/Swiss-Prot entries (release 48.1 of September 27, 2005) have a cross-reference to a PROSITE entry. The database is accessible at .
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                Author and article information

                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central
                1471-2105
                2008
                10 June 2008
                : 9
                : 273
                Affiliations
                [1 ]Université de Rennes I and CNRS UMR 6026, Equipe Structure et Dynamique des Macromolécules, Campus de Beaulieu, Nb 13, 35042 RENNES Cedex, France
                Article
                1471-2105-9-273
                10.1186/1471-2105-9-273
                2442844
                18544157
                a0a438b1-12c5-4930-9766-00c55ba6f486
                Copyright © 2008 Pawlicki et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 June 2007
                : 10 June 2008
                Categories
                Database

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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