8w1z

Structure of a LGR dimer from Caenorhabditis elegans in apo state

spinqualitylabelsall models 8w1z, resolution 3.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8w1z is a 2 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.79Å Ligands: CLR, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G5EG04_CAEEL Publication Abstract from PubMed Glycoprotein hormones (GpHs) produced in the human pituitary act through receptors (GpHRs) in the gonads to support reproduction and in the thyroid for metabolism. GpHs are heterodimeric cystine-knot proteins; their receptors bind cognate hormones at an extracellular domain and signal through a transmembrane domain to heterotrimeric G proteins. GpHs and GpHRs have co-evolved from invertebrate counterparts. Structures of the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers. Here we characterize the homologous receptor from Caenorhabditis elegans. Its biochemical properties are notably similar to those of the thyroid stimulating hormone receptor (TSHR) of humans. Structurally, it is an asymmetric dimer (protomers screw-transformed by 142 degrees /4.1 A), composed such that only one hormone could bind. This is compatible with the 1:2 asymmetry of negatively cooperative TSH:TSHR complexes and for the transactivation evident from functional complementation of binding-deficient and signaling-deficient GpHRs. By modeling, a symmetrized dimer can bind two hormones as in the 2:2 complexes that support TSHR switches in G-protein usage. Structure of an LGR dimer, an evolutionary predecessor of glycoprotein hormone receptors.,Gong Z, Chen S, Fu Z, Kloss B, Wang C, Kim J, Clarke OB, Fan QR, Hendrickson WA Nat Commun. 2025 Nov 28. doi: 10.1038/s41467-025-66676-x. PMID:41315418 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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