Figure 1.
Liganded GPCR, ion channel, and solute carrier protein structures solved by cryo-EM.
(A,B) GPCRs: (A) Ligand-bound GLP-1 structures. Right panel, Structure of GLP-1 signaling complex (PDB 6X19), as solved by Sexton and colleagues [31], bound to CHU-128. Upper left inset, Structure of the ligand-binding pocket of GLP-1R bound to PF-06882961 [31]. Middle left inset, Structure of the ligand-binding pocket of GLP-1R bound to CHU-128. Lower left inset, Structures of the ligand-binding pocket of GLP-1R bound to LY3502970 [95]. (B) CCL20 peptide-bound CCR6 structure. Left panel, Cartoon representation of CCR6-G protein complex bound to CCL20 (PDB 6WWZ). Right inset, CCR6-CCL20 interaction interface with key interacting residues indicated. (C,D) Ion channels: (C) Econazole-bound structure of TRPV5 channel. Right panel, Structure of tetrameric TRPV5, colored by domain, bound to econazole (PDB 6B5V). Upper left inset, TRPV5 calcium-binding selectivity filter, colored by subunit, formed by D542 (shown in stick representation) from each subunit. Bound calcium ion is indicated in green and econazole shown in blue stick representation. Lower left inset, Econazole binding site. Side chains within 4.0 Å of the ligand during MD simulations are labeled and shown as sticks. (D) Liganded structures of TRPV2 channel. Left panel, Cryo-EM map for TRPV2 tetramer (EMD-20686) state 1 bound to cannabidiol (CBD), with a single subunit colored in violet and other subunits in gray. Upper right inset, Close-up of CBD binding site, with TRPV2 model cartoon (PDB 6U8A) shown in violet and CBD in space-filling representation shown in green. Residues forming the ion pore are indicated. Lower right inset, Piperlongumine binding site of TRPV2 (PDB 6WKN [53]), with TRPV2 cartoon colored by subunit and piperlongumine in stick representation. Key interacting residues are shown as sticks. (E–G) Solute carriers: (E) Substrate-bound structure of SLC1A5. Upper panel, Cryo-EM map for SLC1A5 trimer bound to glutamate (EMD-9188), with one subunit highlighted in green. Lower inset, Glutamate binding site of SLC1A5 in the outward-facing conformation (PDB 6MPB), with protein shown as cartoon in green, with glutamate in violet and interacting residues shown as sticks. (F) Structure of ligand-bound NaCT. Upper panel, Cryo-EM map of dimeric NaCT-PF-2 complex (EMD-22456), with one subunit colored in purple. Lower inset, Close-up of PF2 binding site, with NaCT shown in cartoon representation (purple, PDB 7JSJ), and compound and sodium ions colored as indicated. (G) Structures of MCT1 stabilized by ligands in outward- and inward-open conformations. Upper panels, Cartoon representations of MCT1 (pink)/basigin-2 (beige) complex in outward-open (left, PDB 6LYY) and inward-open (right, PDB 7CKO) conformations. Lower panels, Close-ups of compound-binding sites in outward-open (left, compounds superimposed and colored as indicated) and inward-open (right) states.