9K1C
Cryo-EM structure of the DHA bound FFA1-Gi complex
Summary for 9K1C
| Entry DOI | 10.2210/pdb9k1c/pdb |
| EMDB information | 61971 |
| Descriptor | Free fatty acid receptor 1, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (5 entities in total) |
| Functional Keywords | gpcr, ffar1, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 123724.44 |
| Authors | |
| Primary citation | Ke, Y.,Huang, Y.,Yi, C.,Ma, L.,Chu, X.,Wu, B.,Zhao, Q.,Han, S. Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2. Cell Rep, 43:115024-115024, 2024 Cited by PubMed Abstract: Free fatty acid receptors (FFARs) play critical roles in metabolic regulation and are potential therapeutic targets for metabolic and inflammatory diseases. A comprehensive understanding of the activation mechanisms and endogenous ligand selectivity of FFARs is essential for drug discovery. Here, we report two cryoelectron microscopy structures of the human FFAR1 bound to the endogenous ligand docosahexaenoic acid (DHA) and G protein as well as FFAR2 in complex with butyrate and G at 3.2 Å and 3.3 Å resolution, respectively. These structures highlight that distinct locations and sizes of the orthosteric ligand binding pockets are crucial determinants of the endogenous ligand selectivity of this receptor subfamily. Additionally, computational analysis reveals a potential allosteric ligand binding pocket in FFAR2. Furthermore, we observe that the upward movement of helix V upon endogenous ligand binding is responsible for receptor activation. These insights will significantly aid in the development of drugs targeting this receptor family. PubMed: 39616615DOI: 10.1016/j.celrep.2024.115024 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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