Characterizing the Direct Influence of a Small Molecule on a RAS-Related Protein Interaction

Abstract

of Yoda1, a small molecule Piezo1 activator, and identify stretch-induced conformational rearrangements of the blades. Yoda1 binding uncouples two adjacent Piezo repeats, facilitating stretch-induced blade motions, and alters long-range residue-residue contacts between pore and blades, as evidenced by Yoda1-induced channel activation of a mechanically-insensitive mutant. In addition, cation-selective fenestrations allow potassium, not chloride, ions to enter a pore vestibule. Our work reveals the structural bases of cationic selectivity, chemical modulation and mechanical sensing in a mammalian Piezo channel.