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Vasoactive intestinal polypeptide receptor 2 (VIP2R) is involved in immunity. Here, the authors report two cryo-EM structures of the VIP2R–Gs in complex with the endogenous peptide ligand PACAP27, revealing a unique interaction mode between PACAP27 and the receptor, stabilized by the N-terminal α-helix of VIP2R.

Multi-targeting agonists at GIPR, GLP-1R or GCGR are pursued vigorously. Here, the authors report cryo-EM structures of tirzepatide-bound GIPR and GLP-1R, peptide 20-bound GIPR, GLP-1R and GCGR, revealing the molecular basis of their multiplexed pharmacological actions.

IL-6 is an important cytokine in the tumour microenvironment, but its role in regulating autophagy in cancer cells is unclear. Here the authors show that IL-6 activates autophagy in colorectal cancer through the interaction between JAK2 and autophagy regulator, BECN1, which leads to chemotherapeutic resistance.

How the brain represents 3D space is poorly understood but important for understanding spatial cognition. Here the authors record place cells in rats climbing through a 3D environment and report that they represent this space with 3D fields that are elongated along the axes of the environment and encode the vertical dimension less accurately.