GPCRs
Summary
GPCRs (G protein-coupled receptors) are seven-transmembrane-helix receptors that, when a ligand binds, activate an associated G protein by swapping GDP for GTP. The G protein then changes an effector such as adenylyl cyclase or phospholipase C, producing second messengers like cAMP, IP₃ and DAG.
Detail
Meaning: A GPCR is a membrane receptor that crosses the bilayer seven times. Ligand binding (epinephrine, many peptide hormones, odorants) changes the receptor's shape, so it activates a heterotrimeric G protein (Gα, Gβ, Gγ). Gα exchanges GDP for GTP and separates from Gβγ. Gα-GTP (and sometimes Gβγ) then alters an effector enzyme. Gαs activates adenylyl cyclase, raising cAMP, which activates protein kinase A. Gαi inhibits adenylyl cyclase. Gαq activates phospholipase C, which splits PIP₂ into IP₃ (releases Ca²⁺ from the ER) and DAG (activates protein kinase C). The signal ends when Gα hydrolyzes its bound GTP to GDP and rejoins Gβγ.
On the MCAT: Passages describe a hormone whose effect is traced through cAMP or Ca²⁺. You predict what happens to cAMP if Gαs is stuck active, if a GTP analog that cannot be hydrolyzed is added, or if the receptor is blocked. Expect questions on signal amplification (one receptor activates many G proteins, and each enzyme makes many second messengers) and on comparing GPCRs with receptor tyrosine kinases and ligand-gated ion channels.
Common confusion: The GPCR itself is not an enzyme; the G protein and its effector do the work. G proteins bind GTP, not ATP. Heterotrimeric G proteins are also different from small G proteins such as Ras, which act downstream of receptor tyrosine kinases.
Sources
- Molecular Biology of the Cell
- Campbell Biology
- Lehninger Principles of Biochemistry
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.