Structural basis for regulation of CELSR1 by a compact module in its extracellular region
Bandekar, S. J.; Garbett, K.; Kordon, S. P.; Dintzner, E.; Li, J.; Shearer, T.; Sando, R.; Arac, D.
Show abstract
The Cadherin EGF Laminin G seven-pass G-type receptor subfamily (CELSR/ADGRC) is one of the most conserved among adhesion G protein-coupled receptors and is essential for animal development. The extracellular regions (ECRs) of CELSRs are large with 23 adhesion domains. However, molecular insight into CELSR function is sparsely available. Here, we report the 3.8 [A] cryo-EM reconstruction of the mouse CELSR1 ECR and reveal that 14 domains form a compact module mediated by conserved interactions majorly between the CADH9 and C-terminal GAIN domains. In the presence of Ca2+, the CELSR1 ECR forms a dimer species mediated by the cadherin repeats putatively in an antiparallel fashion. Cell-based assays reveal the N-terminal CADH1-8 repeat is required for cell-cell adhesion and the C-terminal CAHD9-GAIN compact module can regulate cellular adhesion. Our work provides molecular insight into how one of the largest GPCRs uses defined structural modules to regulate receptor function.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structure of an LGR dimer - an evolutionary predecessor of glycoprotein hormone receptors 97%
- Structural basis of undecaprenyl phosphate glycosylation leading to polymyxin resistance in Gram-negative bacteria 97%
- Structural Insights into the Venus flytrap Mechanosensitive Ion Channel Flycatcher1 97%
Similar papers in this journal
Similar papers in this journal
- Structural Insights into Cir-mediated Killing by the Antimicrobial Protein Microcin V 96%
- Structure of the Human ATAD2 AAA+ Histone Chaperone Reveals Mechanism of Regulation and Inter-subunit Communication 96%
- Hexokinase-I directly binds to a charged membrane-buried glutamate of mitochondrial VDAC1 and VDAC2 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.