J. Am. Chem. Soc. https://doi.org/10.1021/jacs.9b03927 (2019)

Some intrinsically disordered protein domains have recently been found to sense the curvature of membranes, such as those in endocytic pits and tubular organelles. To define the mechanisms by which disordered domains sense membrane curvature, Zeno et al. tested a series of disordered segments within the C-terminal domain (CTD) of the endocytic protein AP180 for binding to small vesicles of increasing diameter (decreasing curvature). They first found that decreasing the chain length of the AP180 segment reduced curvature sensitivity, consistent with the lower conformational entropy of shorter chains. However, the decrease in free energy was weaker than would be expected if curvature sensing arises only from increases in conformational entropy, hinting that electrostatic effects could also be in play. By varying the ionic strength of the solution, the authors could indeed tune the degree of repulsion between the negatively charged lipids of the vesicles and the substantial net negative charge in AP180CTD to conclude that minimizing electrostatic effects can drive curvature sensing. These results suggest an interplay between entropic effects that are driven by reducing restriction on protein conformation and electrostatic effects to minimize protein–membrane repulsion in sensing membrane curvature.

Credit: ACS