8W1Z
Structure of a LGR dimer from Caenorhabditis elegans in apo state
Summary for 8W1Z
| Entry DOI | 10.2210/pdb8w1z/pdb |
| EMDB information | 43735 |
| Descriptor | G-protein coupled receptors family 1 profile domain-containing protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHOLESTEROL (3 entities in total) |
| Functional Keywords | glycoprotein hormones, glycoprotein hormone receptors, leucine-rich-repeat-containing gpcrs (lgrs), caenorhabditis elegans, dimer, cryo-em., membrane protein |
| Biological source | Caenorhabditis elegans |
| Total number of polymer chains | 2 |
| Total formula weight | 160439.37 |
| Authors | |
| Primary citation | Gong, Z.,Chen, S.,Fu, Z.,Kloss, B.,Wang, C.,Kim, J.,Clarke, O.B.,Fan, Q.R.,Hendrickson, W.A. Structure of an LGR dimer, an evolutionary predecessor of glycoprotein hormone receptors. Nat Commun, 2025 Cited by PubMed Abstract: 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°/4.1 Å), 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. PubMed: 41315418DOI: 10.1038/s41467-025-66676-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.79 Å) |
Structure validation
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