GPCRs, G-proteins, effectors and their interactions: human-gpDB, a database employing visualization tools and data integration techniques

Abstract

G-protein coupled receptors (GPCRs) are a major family of membrane receptors in eukaryotic cells. They play a crucial role in the communication of a cell with the environment. Ligands bind to GPCRs on the outside of the cell, activating them by causing a conformational change, and allowing them to bind to G-proteins. Through their interaction with G-proteins, several effector molecules are activated leading to many kinds of cellular and physiological responses. The great importance of GPCRs and their corresponding signal transduction pathways is indicated by the fact that they take part in many diverse disease processes and that a large part of efforts towards drug development today is focused on them. We present Human-gpDB, a database which currently holds information about 713 human GPCRs, 36 human G-proteins and 99 human effectors. The collection of information about the interactions between these molecules was done manually and the current version of Human-gpDB holds information for about 1663 connections between GPCRs and G-proteins and 1618 connections between G-proteins and effectors. Major advantages of Human-gpDB are the integration of several external data sources and the support of advanced visualization techniques. Human-gpDB is a simple, yet a powerful tool for researchers in the life sciences field as it integrates an up-to-date, carefully curated collection of human GPCRs, G-proteins, effectors and their interactions. The database may be a reference guide for medical and pharmaceutical research, especially in the areas of understanding human diseases and chemical and drug discovery.Database URLs: http://schneider.embl.de/human_gpdb; http://bioinformatics.biol.uoa.gr/human_gpdb/

Identification of G protein-coupled receptor signaling pathway proteins in marine diatoms using comparative genomics

“…Genomic matches were then searched against the respective diatom EST library. Based on sequence similarity to human proteins from the human gpDB database [21], all four diatoms have genes coding for core components of the GPCR signaling pathway. These putative proteins share approximately 25-50% sequence identity to human GPCR pathway proteins when considering alignment lengths >100 aa (Figure  2 and Additional file 1: Table S1).…”

“…The human gpDB is a curated collection of human GPCRs, G proteins, effectors and their interactions [21], collectively referred to here as GPCR signaling pathway proteins. Table  1 lists the key GPCR signaling pathway proteins included in this study.…”

GPCR & Company: Databases and Servers for GPCRs and Interacting Partners

“…The interaction between GPCRs and GIPs creates larger GPCR-associated protein complexes, placing the GPCRs at the center of protein networks that participate in the dynamic regulation of the receptor (Daulat et al 2009;Ritter and Hall 2009). GIPs databases and servers deal with Gproteins (Elefsinioti et al 2004;Satagopam et al 2010;Theodoropoulou et al 2008) and PDZ domains (Beuming et al 2005), and these are summarized in Table 9.4 and described below.…”

“…In addition, the Gprotein's subunits activate or inhibit a variety of effector proteins that modulate the cellular signal-transduction functions (Bosier and Hermans 2007;Wettschureck and Offermanns 2005). Two databases are available for G-protein complexes: the general gpDB (Elefsinioti et al 2004;Theodoropoulou et al 2008) and the more recent Human-gpDB (Satagopam et al 2010). Both provide information on the coupling between GPCR and G-protein ' subunit and on the interactions between the G-protein subunits and different effectors, and supply additional information on the interacting partners.…”

“…The human-gpDB allows 2D and 3D visualization of the network of connections between GPCRs, related drugs, G-proteins and effectors. It also offers links to many additional GPCR web resources (Satagopam et al 2010).…”