Closeup of M2NX peptide binding to the ADPR site of human TRPM2
Global view of the peptide binding to the protein
Marmoset render of ADPR binding site
Interactive version
Interactive Version - No labels
Alternate viewpoint of the intermolecular interactions without the ribbon
Alternate viewpoint of the intermolecular interactions without the ribbon
Additional interactions formed by the TAT tag
Final manuscript figure. Residues belonging to the peptide are in bold. Dashed lines indicate non-bond interactions (pink = hydrophobic, green = hydrogen bonds, white = carbon-hydrogen bonds, orange = electrostatic interactions).
Manuscript figure showing the initial predicted binding of the peptide (left) and the complex after 5 nanoseconds (ns) of explicit solvent-based molecular dynamics (MD) simulation. The ADPR binding site is on the left (white arrowhead).
Supplementary manuscript figure showing that only TRPM2 contains the ADPR binding site (red arrow), suggesting that the M2NX peptide would not inhibit the other members of the TRPM family.
Transient receptor potential cation channel, subfamily M, member 2 (TRPM2) is a calcium channel in neurons that is activated by adenosine diphosphate ribose (ADPR) or oxidative stress. TRPM2 contributes to neuronal injury in the brain caused by stroke and cardiac arrest (among other diseases). Dr. Paco Herson, PhD, et al, have developed a peptide inhibitor M2NX fused to a cell-penetrating TAT tag that prevents ligand binding and TRPM2 activation. Tryptophan 33 (W33) and Valine 34 (V34) are critical for peptide binding to the ADPR site of TRPM2. Figures rendered in Lightwave 2019 or Marmoset Toolbag 3.08. I performed all of the molecular modeling simulations and generated all of the figures. For more information see https://www.ncbi.nlm.nih.gov/pubmed/31772034, the article is free to read.
