The structure of a nanobody-stabilized active state of the β2 adrenoceptor was determined by researchers, revealing key insights into the conformational changes that occur during agonist binding and receptor activation. The study utilized a camelid antibody fragment (nanobody) that mimics the behavior of G proteins, allowing for the stabilization of an active conformation of the β2 adrenoceptor (β2AR). This structure was compared with the inactive β2AR structure, showing subtle changes in the binding pocket and significant rearrangements of transmembrane segments 5 and 7, similar to those observed in opsin, an active form of rhodopsin. The β2AR, a G protein-coupled receptor (GPCR), exhibits a range of functional states in response to ligands. The study highlights the challenges in capturing the active state of GPCRs in a crystal structure due to their inherent instability. The nanobody-stabilized active state of β2AR was found to be similar to the conformation stabilized by G proteins, suggesting that the nanobody acts as a surrogate for G proteins in stabilizing the active state. The study also identified BI-167107 as a high-affinity agonist for β2AR, which induces significant conformational changes in the receptor. The crystal structure of the β2AR-T4L-Nb80 complex was determined, revealing structural changes in the transmembrane segments that facilitate agonist binding and receptor activation. These changes are similar to those observed in rhodopsin and opsin, indicating a conserved mechanism of G protein activation. The study provides a detailed structural analysis of the β2AR in its active state, highlighting the importance of specific interactions in stabilizing the active conformation. The findings contribute to the understanding of the structural basis for the functional versatility of GPCRs and offer insights into the mechanisms of agonist binding and activation. The results also demonstrate the utility of nanobodies in stabilizing and studying the active states of GPCRs, which could have implications for drug development and the treatment of diseases involving GPCR signaling.The structure of a nanobody-stabilized active state of the β2 adrenoceptor was determined by researchers, revealing key insights into the conformational changes that occur during agonist binding and receptor activation. The study utilized a camelid antibody fragment (nanobody) that mimics the behavior of G proteins, allowing for the stabilization of an active conformation of the β2 adrenoceptor (β2AR). This structure was compared with the inactive β2AR structure, showing subtle changes in the binding pocket and significant rearrangements of transmembrane segments 5 and 7, similar to those observed in opsin, an active form of rhodopsin. The β2AR, a G protein-coupled receptor (GPCR), exhibits a range of functional states in response to ligands. The study highlights the challenges in capturing the active state of GPCRs in a crystal structure due to their inherent instability. The nanobody-stabilized active state of β2AR was found to be similar to the conformation stabilized by G proteins, suggesting that the nanobody acts as a surrogate for G proteins in stabilizing the active state. The study also identified BI-167107 as a high-affinity agonist for β2AR, which induces significant conformational changes in the receptor. The crystal structure of the β2AR-T4L-Nb80 complex was determined, revealing structural changes in the transmembrane segments that facilitate agonist binding and receptor activation. These changes are similar to those observed in rhodopsin and opsin, indicating a conserved mechanism of G protein activation. The study provides a detailed structural analysis of the β2AR in its active state, highlighting the importance of specific interactions in stabilizing the active conformation. The findings contribute to the understanding of the structural basis for the functional versatility of GPCRs and offer insights into the mechanisms of agonist binding and activation. The results also demonstrate the utility of nanobodies in stabilizing and studying the active states of GPCRs, which could have implications for drug development and the treatment of diseases involving GPCR signaling.