GPCRDB: information system for G protein-coupled receptors

Abstract

The GPCRDB is a Molecular Class-Specific Information System (MCSIS) that collects, combines, validates and disseminates large amounts of heterogeneous data on G protein-coupled receptors (GPCRs). The GPCRDB contains experimental data on sequences, ligand-binding constants, mutations and oligomers, as well as many different types of computationally derived data such as multiple sequence alignments and homology models. The GPCRDB provides access to the data via a number of different access methods. It offers visualization and analysis tools, and a number of query systems. The data is updated automatically on a monthly basis. The GPCRDB can be found online at http://www.gpcr.org/7tm/.

Figure 1.

Screenshot of the principal protein sequence page of the human beta-2 adrenoceptor. The top table contains details about the protein record and hyperlinks to the protein family browsing page and other data sources that contain information about this protein. The middle table holds the sequence in which each amino acid is linked to its own residue page. The bottom table holds annotations that are obtained in real time using the DAS (15) system.

Figure 2.

Screenshot of the interactive entropy and variability page. The multiple sequence alignment is shown in (A). Residues are interlinked in all page elements, clicking results in highlighted selections. In (B), the approximate location of this position in the 3D model of the transmembrane domain of class A GPCRs is shown in red and is annotated with general residue number information. The orange ball in the structure model indicates the approximate location of the assumed binding site for low molecular weight compounds of class A GPCRs. In (C) the user can choose among four display modes that describe the entropy and variability of all positions in the alignment; shown is the entropy cluster variant.

Figure 3.

Screenshot of the GPCR family page. The GPCR family tree is shown on the left with the amine sub-family expanded. On the right-hand side the data for the selected family (adrenoceptors) is shown.

Figure 4.

Snake plot of the human β2 adrenoceptor.

Figure 5.

Screenshot of the detail page of residue W175 in OPSD_HUMAN. Residue numbers in different formats are shown, the approximate location of the residue is visually indicated and available mutations and oligomer data for this residue are listed.

Figure 6.

The protein search page.

Figure 7.

A list of proteins and an optional list of residue positions can be used to generate custom alignments. In this figure we have selected a number of proteins for which crystal structures are available. The GPCR-binding pocket residue positions as proposed by Gloriam et al. (42) are used. The result will be an alignment of all pocket residues of the selected proteins.

Figure 8.

An impression of the PDF reader [Utopia Documents (43), Utopia Documents-GPCRDB (in preparation)] interface to the GPCRDB data. On the left side (A) a scientific paper (44) is shown that is annotated by the GPCRDB. Annotations are available for all the highlighted words. On the right side (B) an example of such an annotation (the mutation F339L) is displayed. A short, manually extracted description of the effects of this mutation is included (C).