Fig. 8: Probenecid-induced conformational changes.
From: Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function
a Cryo-EM maps of TRPV2probenecid at 3.5 Å overall resolution with one subunit shown in magenta and the remaining subunits in grey. b The profile of the ion permeation pathway, displayed as grey space-filling model, (left) and the corresponding calculated pore radius as a function of the distance along the ion conduction pathway (right) for TRPV2probenecid (magenta). The pore radii of TRPV2OPEN (PDB-ID:6BO4; black line) and TRPV2apo-1 (PDB-ID: 6U84; pink line) are also included as references. c, d Overlay of (c) TRPV2probenecid (magenta) and TRPV2 C16-1 (light green) and (d) TRPV2probenecid TRPV2C16-2 (dark green) structures based on the alignment of a single subunit. Residues of interest are labelled and represented as sticks. Also shown are PC (c) and CHS (d) as yellow sticks, C16 (d) as pink sticks. e-g Overlay of globally aligned TRPV2probenecid (magenta) and TRPV2apo-1 (pink). e Membrane view comparisons of opposite pore-forming subunits. f Membrane view of the transmembrane region of a single subunit illustrating the differences in the vanilloid pocket region. g View of the pore from the intracellular side of the membrane. PH indicates pore helix, and arrows indicate structural movements of TRPV2probenecid in relation to TRPV2apo-1. The length of the arrow displays the varying degrees of structural changes. Star indicates local conformational changes.
