Fig. 1: Cryo-EM model of ADGRL3/LK3 complex reveals the general architecture of the receptor and relative position of the GAIN domain in relation to the transmembrane region.

a Cartoon representation of ADGRL3. The lectin domain is colored red, olfactomedin - orange, HormR - purple, GAIN - green, and 7TM in blue. The tethered agonist (TA) is presented as a black arrow within the GAIN domain. b Schematic diagram of domain boundaries of the ADGRL3 construct used for structural analysis. Domains colored as in (a). GPS represents GPCR Proteolysis Site. c Representative cryo-EM reference-free 2D class averages of the ADGRL3/LK3 complex purified in detergent micelle. d 6 Å low-pass filtered 3D map of ADGRL3 in complex with sAB LK3 at the threshold level set to 0.0375. Regions of the map corresponding to respective domains of the receptor and sAB are colored accordingly and labeled with domain names. The tethered agonist (TA) is colored magenta. e The composite map of ADGRL3 architecture consisting of a 3.9 Å structure of the HormR/GAIN domain in complex with sAB LK3, and a 6 Å low-pass filtered density for the micelle. f Proposed composite model of ADGRL3 holoreceptor. The hypothetical location of 7TM (available structure of apo-state ADGRL3 corresponding to PDB: 8jmt) is placed in the membrane region.