7D3S

Human SECR in complex with an engineered Gs heterotrimer

Summary for 7D3S

• Entry DOI: 10.2210/pdb7d3s/pdb
• EMDB information: 30566
• Descriptor: Secretin, Secretin receptor, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
• Functional Keywords: class b gpcr, secretin, secr, signaling protein-hormone complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 158351.31

Authors

Fukuhara, S.,Kobayashi, K.,Kusakizako, T.,Shihoya, W.,Nureki, O. (deposition date: 2020-09-20, release date: 2020-11-04, Last modification date: 2024-11-13)

Primary citation

Fukuhara, S.,Kobayashi, K.,Kusakizako, T.,Iida, W.,Kato, M.,Shihoya, W.,Nureki, O.
Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein.
Biochem.Biophys.Res.Commun., 533:861-866, 2020

PubMed Abstract: Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications.

PubMed: 33008599
DOI: 10.1016/j.bbrc.2020.08.042

Experimental method

ELECTRON MICROSCOPY (2.9 Å)