9OXA

CryoEM structure of Gi-coupled TAS2R43 with aristolochic acid I

Summary for 9OXA

• Entry DOI: 10.2210/pdb9oxa/pdb
• EMDB information: 70964
• Descriptor: Soluble cytochrome b562,Taste receptor type 2 member 43, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (7 entities in total)
• Functional Keywords: gpcr, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 192352.36

Authors

Kim, Y.,Gumpper, R.H.,Roth, B.L. (deposition date: 2025-06-03, release date: 2026-04-22, Last modification date: 2026-05-06)

Primary citation

Kim, Y.,Gumpper, R.H.,Zhuang, Y.,Dror, R.O.,Roth, B.L.
Structural insights into coffee bitter taste perception by TAS2R43 receptor.
Nat.Struct.Mol.Biol., 33:701-710, 2026

PubMed Abstract: Bitter taste functions as a means of both protection against potentially toxic compounds and savoring bitter tasting foods and beverages. Among the 26 bitter taste receptors, taste receptor type 2 member 43 (TAS2R43) has been identified as key for recognizing the bitter taste of coffee. TAS2R43 has also been implicated in many other physiological processes, including the regulation of glucagon-like peptide 1 release from the intestine, bronchodilation, innate immunity and metabolism. Here we report cryo-electron microscopy structures of human TAS2R43 coupled with inhibitory G protein or gustducin (G) stabilized by the potent nephrotoxin and carcinogen aristolochic acid I. Both structures revealed that aristolochic acid I binds in a presumed orthosteric pocket shared with other bitter taste receptor. Further structural, functional and computational studies revealed potential modes for coffee's constituents including caffeine and cafestol, which are bitter tastants from coffee. Lastly, long-timescale molecular dynamics simulations identified potential cryptic allosteric pockets in TAS2R43. These structures could accelerate the search for specific bitter taste ligands that ultimately may be therapeutically useful.

PubMed: 42009777
DOI: 10.1038/s41594-026-01776-w

Experimental method

ELECTRON MICROSCOPY (2.9 Å)