| Description |
Somatostatin receptors play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non peptide agonist, respectively, a cryo electron microscopy structure of Gi1 bound SSTR2 in the presence of the endogenous ligand SST 14, as well as two cryo EM structures of Gi1 bound SSTR4 in complex with SST 14 and a small molecule agonist J2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. |