Cell Surface Receptor(s)
Cell surface receptors, often called transmembrane receptors, are important proteins that mediate communication between the cell and the outside world. Extracellular ligands (cytokines, growth factors, hormones, neurotransmitters, or cell recognition molecules) bind to the receptor, triggering conformational changes that initiate intracellular signaling pathways (signal transduction). Cell surface receptors regulate a multitude of biological pathways required for cell growth, differentiation, proliferation, and survival.
Because of the critical nature of these pathways, it is not surprising that mutations in cell surface receptors are responsible for a wide array of diseases, including cancers, neurodegeneration, achondroplasia and atherosclerosis. In fact, nearly half of all drugs in clinical use target cell surface receptors, and these proteins and their ligands remain extremely important targets for structure-based drug design and novel drug development.
Cell Surface Receptors are divided into 3 major classes: ion channel-linked receptors, enzyme-linked receptors, and G protein-coupled receptors.
Ion channels are pore-forming proteins present in the membranes of all cells. Ions pass through channels down their electrochemical gradient, without the requirement for ATP or metabolic energy. Ion channels are especially prominent components of the nervous system, since "transmitter-activated" channels mediate conduction across nerve synapses. Ion channels are also key components in the cellular response to toxins and venoms, as well as biological processes that involve rapid changes in cells, such as cardiac, skeletal, and smooth muscle contraction, T-cell activation and hormone release.
Enzyme-linked receptors are usually single-pass transmembrane receptors. This group includes the highly studied receptor tyrosine kinases (RTKs), which bind to polypeptide growth factors that control cell proliferation and differentiation. Also included are receptor serine/threonine kinases, receptor-like tyrosine phosphatases, and receptor guanylyl cyclases that catalyze the production of cyclic GMP in the cytosol.
G-protein-coupled receptors (GPCRs), also known as 7 transmembrane (7-TM) receptors, are structurally and functionally related proteins characterized by seven membrane-spanning a helices. GPCRs are involved in numerous signaling pathways, including sensory perception (sight, smell, taste, pain). GPCRs are also activated by many neurotransmitters, neuropeptides, and peptide hormones.
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