Lecture Six: GPCR

This lecture focuses on the structure, function, and subtypes of a particular receptor called G-protein coupled receptor (GPCR). The GPCR is bound to the G-protein. A discussion of its active and inactive states is reviewed where in order to be active, it requires the enzyme GTPase to promote the phosphorylation of the bound guanosine diphosphate (GDP) to guanosine triphosphate (GTP). To understand how GPCR transduces the signal in the cell using a second messenger called cAMP and downstream signaling pathway. cAMP stimulates the enzyme protein kinase A (PKA) by binding to one of the PKA subunits (regulatory). PKA targets cAMP response element-binding protein (CREB) and phosphorylates CREB to induce transcription of target genes and illicit response. Other PKA targets are also discussed in this lecture. There are a range of cellular responses: proliferation, survival, metabolism, differentiation, movement, sensory perception, hematopoiesis, neural transmission, apoptosis, immune response, memory, and learning. To discover the causes of the dysregulation of the GPCR pathway that results in various types of cancer and other non-communicable diseases, for instance, cardiovascular disease and asthma. The G-protein independent pathway covered where ions such as Bicarbonate and calcium promote the synthesis of cAMP synthesis without G proteins.

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Structure Of The GPCR

This image presents the structure of GPCR. It is a cell surface receptor with three main regions: extracellular, intracellular, and transmembrane. Amongst the common ligands are amino acids, hormones, small ions, proteins, and neurotransmitters. The extracellular loop region (ECR) is where the ligand joins with the receptor whereas, the intracellular membrane loop (ICR) is where signal transduction occurs. The intracellular loops have defined roles, for instance, C4 is a phosphorylation site, whereas, C3 interacts with G-proteins. The transmembrane region joins ECR and ICR together and consists of seven proteins with a helical shape. The helical shape (dark blue) helps with internal and external communication. Most GPCRs have seven helices and three intracellular loops, however, one type of GPCR, for instance, rhodopsin has eight helices and four intracellular loops. The G proteins have three different subunits [Gα (lime green), Gβ (light orange), and Gγ (orange)] hence it is referred to as a heterotrimer. Hetero = different. Trimer – three subunits. G proteins are classified according to their α subunit; Gαi, Gαs, Gα12/13, and Gαq. A larger size can be found in the resource list.