Lecture 5 - GPCRs I Flashcards
What are the two main types of receptors in the nervous system?
Ionotropic receptors (ligand-gated ion channels) and metabotropic receptors.
What is the difference between ionotropic and metabotropic receptors?
Ionotropic receptors allow for direct exchange of ions through a pore in the ion channel, while metabotropic receptors are indirectly linked to ion channels through signal transduction mechanisms such as G proteins.
What are the structural features of G protein-coupled receptors (GPCRs)?
GPCRs have seven transmembrane domains (TMs) and the N-terminus is at the extracellular side (ligand binding), while the C-terminus is at the intracellular side (G protein binding).
What is the mechanism of action for G protein-coupled receptors (GPCRs)?
GPCRs are activated by ligand binding, which causes a conformational change in the receptor that activates the G protein. The alpha subunit of the G protein then separates from the beta-gamma subunit and binds to GTP, becoming active. The alpha subunit then binds to a target protein to elicit a cellular response.
What are G proteins and how do they function as molecular switches?
G proteins are guanine nucleotide-binding proteins that act as molecular switches inside the cell to transmit signals from extracellular stimuli. They are regulated by the ability to bind and hydrolyze GTP (‘on’) to GDP (‘off’).
What are second messengers and why are they important in G protein signaling?
Second messengers are small molecules that carry signals inside cells. They include hydrophobic lipids confined to the membrane in which they are generated, small soluble molecules that diffuse through the cytoplasm (cAMP, cGMP), and calcium ions. Second messenger systems are necessary to phosphorylate and activate millions of proteins as a result of a single ligand binding to a single GPCR.
What is the mechanism of action for activated G proteins?
Activated G proteins can regulate the activities of enzymes that control the levels of second messengers, such as cAMP, cGMP, and calcium ions. They can also directly activate ion channels or enzymes that create second messengers.
What is the importance of G protein diversity?
G protein diversity contributes to the diversity of receptors and allows multicellular organisms to respond to the vast amount of environmental stimuli.
What are some examples of mutations in GPCRs and their implications?
Uveal melanoma - GNAQ and GNA11: Over 90% of uveal melanoma cases have mutations in the Gq α subunit, which lead to blocking of GTP hydrolysis. The alpha subunit remains always active, causing permanent signal transmission and constitutively active growth pathways.
