Abstract
Recent studies on G protein-coupled receptors (GPCRs) dynamics
report that GPCRs adopt a wide range of conformations that
coexist in equilibrium, with the apo state of a GPCR having a
high entropy. The formation of a ligand-GPCR-transducer complex
comes with a reduction of conformational space and therefore with
an entropic cost. We hypothesize that the availability of binding
partners, their binding affinity and the rigidity of the
respective binding sites are reflected in a distinct degree of
sequence conservation to balance the energetic cost of intra- and
extracellular binding events. Here, we outline the current
findings in delineating the conformational space and include
sequential conservation of many-to-many ligand-receptor systems
to discuss the entropic cost that comes with GPCR signal
transduction.
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