Positive cooperativity enhances coupling of a second G protein to a GPCR dimer

Coupling the second G protein to the obligate Ste2 dimer shows an 18-fold higher affinity than coupling the first, revealing strong positive cooperativity between protomers.

• Why it matters: GPCR dimerization can reshape receptor pharmacology, but how sequential G protein recruitment within a dimer changes coupling energetics remains unclear.
• What they did: The study analyzed the class D1 fungal receptor Ste2, which couples two G proteins per dimer, and determined relative affinities for first versus second G protein coupling.
• The result: The data support a mechanism where the first G protein stabilizes the adjacent protomer in an active, pre-formed coupling-site state, enhancing second G protein affinity and suggesting a general oligomerization-linked pharmacology mechanism.

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