7XK8

Cryo-EM structure of the Neuromedin U receptor 2 (NMUR2) in complex with G Protein and its endogeneous Peptide-Agonist NMU25

Summary for 7XK8

• Entry DOI: 10.2210/pdb7xk8/pdb
• EMDB information: 33247
• Descriptor: Neuromedin-U-25, Neuromedin-U receptor 2, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (5 entities in total)
• Functional Keywords: gpcr, complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 134838.01

Authors

Zhao, W.,Wenru, Z.,Mu, W.,Minmin, L.,Shutian, C.,Tingting, T.,Gisela, S.,Holger, W.,Albert, B.,Cuiying, Y.,Xiaojing, C.,Han, S.,Wu, B.,Zhao, Q. (deposition date: 2022-04-19, release date: 2023-02-22)

Primary citation

Zhao, W.,Zhang, W.,Wang, M.,Lu, M.,Chen, S.,Tang, T.,Schnapp, G.,Wagner, H.,Brennauer, A.,Yi, C.,Chu, X.,Han, S.,Wu, B.,Zhao, Q.
Ligand recognition and activation of neuromedin U receptor 2.
Nat Commun, 13:7955-7955, 2022

PubMed Abstract: Neuromedin U receptor 2 (NMU2), an emerging attractive target for treating obesity, has shown the capability in reducing food intake and regulating energy metabolism when activated. However, drug development of NMU2 was deferred partially due to the lack of structural information. Here, we present the cryo-electron microscopy (cryo-EM) structure of NMU2 bound to the endogenous agonist NmU-25 and G at 3.3 Å resolution. Combined with functional and computational data, the structure reveals the key factors that govern the recognition and selectivity of peptide agonist as well as non-peptide antagonist, providing the structural basis for design of novel and highly selective drugs targeting NMU2. In addition, a 25-degree rotation of G protein in reference to NMU2 is also observed compared in other structures of class A GPCR-G complexes, suggesting heterogeneity in the processes of G protein-coupled receptors (GPCRs) activation and G protein coupling.

PubMed: 36575163
DOI: 10.1038/s41467-022-34814-4

Experimental method

ELECTRON MICROSCOPY (3.3 Å)