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Structure paper

TitleStructural basis for ligand recognition and activation of the prostanoid receptors.
Journal, issue, pagesCell Rep, Vol. 43, Issue 3, Page 113893, Year 2024
Publish dateMar 5, 2024
AuthorsXiu Li / Xuan Zhang / Xin Wen / Daolai Zhang / Changxiu Qu / Xinyi Miao / Wenkai Zhang / Ru Zhang / Guibing Liu / Peng Xiao / Jin-Peng Sun / Weimin Gong /
PubMed AbstractProstaglandin F (PGF) and thromboxane A (TXA) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through ...Prostaglandin F (PGF) and thromboxane A (TXA) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through activating PGF receptor (FP) and TXA receptor (TP). Ligands targeting FP and TP have demonstrated efficacy in treating conditions like glaucoma and cardiovascular diseases in humans, as well as reproductive-related diseases in animals. Here, we present five cryoelectron microscopy structures illustrating FP and TP in complex with G and bound to PGF (endogenous ligand), latanoprost acid (a clinical drug), and two other synthetic agonists. Combined with mutational and functional studies, these structures reveal not only structural features for the specific recognition of endogenous ligands and attainment of receptor selectivity of FP and TP but also the common mechanisms of receptor activation and G protein coupling. The findings may enrich our knowledge of ligand recognition and signal transduction of the prostanoid receptor family and facilitate rational ligand design toward these two receptors.
External linksCell Rep / PubMed:38446662
MethodsEM (single particle)
Resolution2.63 - 3.11 Å
Structure data

38399

8xjk

EMDB-38399, PDB-8xjk:
Cloprosetnol bound Prostaglandin F2-alpha receptor-Gq Protein Complex
Method: EM (single particle) / Resolution: 2.63 Å

38400

8xjl

EMDB-38400, PDB-8xjl:
PGF2-alpha bound Prostaglandin F2-alpha receptor-Gq Protein Complex
Method: EM (single particle) / Resolution: 2.77 Å

38401

8xjm

EMDB-38401, PDB-8xjm:
Latanoprost acid bound Prostaglandin F2-alpha receptor-Gq Protein Complex
Method: EM (single particle) / Resolution: 2.85 Å

38402

8xjn

EMDB-38402, PDB-8xjn:
Cloprosetnol bound Thromboxane A2 receptor-Gq Protein Complex
Method: EM (single particle) / Resolution: 3.06 Å

38403

8xjo

EMDB-38403, PDB-8xjo:
U46619 bound Thromboxane A2 receptor-Gq Protein Complex
Method: EM (single particle) / Resolution: 3.11 Å

Chemicals

PDB-1d5a:
CRYSTAL STRUCTURE OF AN ARCHAEBACTERIAL DNA POLYMERASE D.TOK. DEPOSITION OF SECOND NATIVE STRUCTURE AT 2.4 ANGSTROM

ChemComp-UGU:
(Z)-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(E,3S)-3-oxidanyloct-1-enyl]cyclopentyl]hept-5-enoic acid

ChemComp-7WT:
Z-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(3R)-3-oxidanyl-5-phenyl-pentyl]cyclopentyl]hept-5-enoic acid

ChemComp-PUC:
(5Z)-7-{(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-oxabicyclo[2.2.1]hept-5-yl}hept-5-enoic acid

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / cryo-EM / Complex / Signaling Protein

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