GPCR Pipeline | Background Page
G-Protein Coupled ReceptorsG-Protein Coupled Receptors (GPCRs) are a large and diverse superfamily of membrane receptor proteins . GPCRs are characterized by a seven transmembrane structure with an external N-terminus and an internal C-terminus . This leads to the superfamily sometimes being referred to as 7-transmembrane receptors . The cytoplasmic face couples to a heterotrimeric G-protein complex . When the receptor ligand binds to the external face, the G-protein complex dissociates from the receptor . The G-protein alpha-subunit is activated by exchange of GDP for GTP and proceeds to initiate the signaling cascade .
GPCRs are of great interest to researchers as it is estimated that 50-60% of all pharmacological drugs target GPCRs . For example, psuedoephedrine interacts with the adregenergic receptors in order to act as a decongestant . Another example is haldol, which affects dopamine and serotonin receptors and is used in the treatment of schizophrenia . G-protein coupled receptors are prevalent in vision, neurotransmission, immunology, and many other systems [1,2,3].
GPCR ClassificationGPCRs can be classified into several distinct classes. The GRAFS system places the receptors into 5 distinct classes: Glutamate, Rhodopsin-like, Adhesion, Frizzled/Taste2, and Secretin . The GRAFS system applies specifically to vertebrate GPCRs . An alternative classification which applies to both vertebrate and invertebrate GPCRs is the IUPHAR system . The IUPHAR classification is split into the Class A (Rhodopsin-like), Class B (secretin-like), Class C (metabotropic glutamate), Class D (fungal mating pheromone receptors), Class E (cAMP receptors), Class F (frizzled/smoothened) . The classes D and E are unique to invertebrates .
Data retrieved: January 3, 2016
GPCR PipelineOur pipeline utilizes sequence similarity, transmembrane structure, and dipeptide composition to determine if a protein sequence is a GPCR. A BLAST  search determines if a given sequence bears close sequence similarity to known sequences (from the curated Uniref  database), operating under the assumption that sequence similarity may indicate sequence homology. PFAM utilizes protein domain profiles in order to identify families and functional domains . PFAM can also help to determine class as there are several class-specific 7-transmembrane profiles available . 7tm_1 denotes the Rhodopsin-like class, 7tm_2 denotes Secretin-like, 7tm_3 denotes the Glutamate class and several other profiles denote other classes . Additionally, we utilize the conserved 7-transmembrane structure of GPCRs using TMHMM . TMHMM predicts the number of transmembrane helices in a protein sequence using a hidden Markov model . We use this prediction to check that the transmembrane structure of a predicted protein is congruent with GPCR 7-transmembrane structure. Additionally, we use GPCRpred, a SVM which uses the dipeptide composition of a protein sequence to predict whether a protein is a GPCR and which class it belongs to . By combining these various tools and approaches we can make a more accurate prediction as to whether or not a query protein sequence is a GPCR.
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