Sandbox Reserved 1180: Difference between revisions

G protein coupled receptors (GPCRs) are the largest class of integral membrane proteins.  GPCRs are divided into five families; the rhodopsin family (class A), the secretin family (class B), the glutamate family (class C), the frizzled/taste family (class F), and the adhesion family.<ref name= "Zhang 2006"/> Roughly 5% of the human genome encodes g-protein-coupled receptors, which are responsible for the transduction of endogenous signals and the instigation of cellular responses. All GPCRs contain a similar seven α-helical transmembrane domain (TMD or 7TMD) that once bound to its ligand, undergoes a conformational change and tranduces a signal to coupled, heterotrimeric G proteins.  The initiation of intracellular signal pathways occur in response to stimuli such as light, Ca2+, odorants, amino acids, nucleotides, peptides, and other proteins. <ref name= "Zhang 2006">DOI 10.1371/journal.pcbi.0020013</ref>  See also [http://www.http://proteopedia.org/wiki/index.php/Main_Page Wikipedia G protein-coupled receptors]

Class B GPCRs contain 15 distinct receptors for peptide hormones and generate their signal pathway through the activation of adenylate cyclase (AC) which increases concentration of cAMP, inositol phosphate, and calcium levels in cyto. <ref>DOI 10.1111/bph.12689</ref> These signals are essential elements of intracellular signal cascades for human diseases including type II diabetes mellitus, osteoporosis, obesity, cancer, neurological degeneration, cardiovascular diseases, headaches, and psychiatric disorders; making their regulation through drug targeting of particular interest to companies developing novel molecules.  <ref name= "Hollenstein 2014">DOI 10.1016/j.tips.2013.11.001</ref>  Structurally based approaches to the development of small-molecule agonists and antagonists have been hampered by the lack of accurate Class B TMD visualizations until recent crystal structures of corticoptropin-releasing factor receptor 1 and human glucagon were realized. <ref name= "Hollenstein 2013">DOI 10.1038/nature12357</ref> <ref name= "Siu 2013">DOI 10.1038/nature12393</ref>