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G proteins are essential molecular players in the intricate symphony of cellular signaling. From our vision to our sense of smell, neurotransmission to cell growth, G proteins are at the core of these vital processes. To delve into their activation and unlock the potential for targeted therapies, researchers have embarked on a quest to understand the intricate mechanisms at play. A recent paper takes us on this journey, shedding light on how G proteins of different families are allosterically activated, potentially paving the way for the development of specific treatments for a range of diseases. G proteins are heterotrimeric complexes, consisting of α, β, and γ subunits. The α subunit, known as Gα, holds the key to their activation (see figure). In their inactive state, Gα proteins have GDP bound between their G domain and H domain. Activation occurs when G protein-coupled receptors (GPCRs) bind to Gα, prompting the exchange of GDP for GTP, and leading to separation from...

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